Effects of catecholamines on blood pressure in the femoral bone marrow cavity
in ovariectomized rats
Ilona Kaczmarczyk-Sedlak, Urszula Cegie³a, Barbara Nowiñska, Maria Pytlik
Department of Pharmacology, Medical University of Silesia, Jagielloñska 4, PL 41-200 Sosnowiec, Poland Correspondence: Ilona Kaczmarczyk-Sedlak, e-mail: farmak@slam.katowice.pl
Abstract:
Menopausal women display changes in the osseous tissue (osteoporosis, pathologic fractures) and disorders in the function of cardiovascular system (hypertension, cardiovascular disease, arteriosclerosis, calcification). Additionally, interdependence was observed between the loss of osseous tissue and disordered circulation, but the mechanism of the interdependence has never been fully recognized. In order to clarify this problem, the present study concentrated on the effects of catecholamines on blood pressure in the femoral bone marrow cavity in ovariectomized rats. The Ficat-Arlet method was used to examine blood pressure in marrow cavity. Norepinephrine, epinephrine, isoprenaline as well as adrenoceptor antagonists (phentolamine and propranolol) were administered to the controls and the ovariectomized rats. The examinations demonstrated that ovariectomized rats displayed decreased blood pressure in the marrow cavity. In addition, an intensified effect of catecholamines on blood pressure in the marrow cavity of osteoporotic bone in ovariectomized rats was observed.
Key words:
blood pressure, bone, catecholamines, osteoporosis, ovariectomy, rat
Introduction
Blood pressure increases in many postmenopausal women. The mechanisms responsible for the post- menopausal increase in blood pressure are not yet well recognized. Various humoral systems have been proposed to play a role in postmenopausal hyperten- sion, such as changes in estrogen/androgen ratios, ac- tivation of the renin-angiotensin system and increases in endothelin and oxidative stress. Activation of the sympathetic nervous system may also play an impor- tant role in postmenopausal hypertension [28]. Higher blood pressure in postmenopausal women is associ-
ated with an increased bone loss [5, 11, 30]. Similarly in rats, hypertension may contribute to the develop- ment of osteoporosis [22, 25].
Blood flow in bone depends upon the physiological status of the entire circulatory system, but mecha- nisms that regulate intraosseus circulation are not fully understood, probably because they are difficult to studyin vivo. It has also been recognized that cyto- kines and growth factors which regulate intraosseus angiogenesis, also regulate bone remodeling. Most diseases characterized by increased bone resorption (for example osteoporosis) are associated with in- creased bone vascularization [19].
Pharmacological Reports 2006, 58, 908919 ISSN 1734-1140
Copyright © 2006 by Institute of Pharmacology Polish Academy of Sciences
In order to explain the interdependence between osteoporosis and blood circulation in bone, the authors of this study decided to investigate the effects of catecholamines on blood pressure in the femoral marrow cavity in ovariectomized rats.
Materials and Methods
The experiments were carried out on three-month-old female Wistar rats (210–220 g). The permission for the animal tests and experiments has been given by the Bioethical Board of the Silesian Medical University.
The animals were divided into 2 groups, 30 ani- mals each, according to the type of surgical operation they underwent: I (C) – control sham operated rats; II (OVX) – ovariectomized rats. Bilateral ovariectomy or sham-operation was performed under ether anes- thesia. A longitudinal incision was made inferior to the rib cage on the dorsolateral body wall. The ovaries were exteriorized, ligated and excised. Rats subjected to the sham surgical procedure had only the ovaries exteriorized and then replaced.
The animals in each of the two main groups (C and OVX) were additionally divided into five subgroups administerediv adrenoceptor agonists and antagonists (Tab. 1).
Catecholamines norepinephrine (NE), epinephrine (E), isoprenaline (IP) were administered at increasing doses at 10-min intervals. Subsequently, phentola- mine (PHT) or propranolol (PR) was administered,
and 5 min later the appropriate catecholamine was readministered every 10 min at increasing doses.
After the lapse of 4 weeks from the time of surgical removal of ovaries, the animals (C and OVX groups) were anesthetized with urethane at the dose of 1.9 g/kg,ip. To prevent blood clotting, the animals re- ceived an iv injection of heparin at the dose of 2,000 IU/kg.
Arterial blood pressure was measured in the left ca- rotid artery by inserting a polyethylene cannula into the artery, which through a membrane sensor was connected to a pressure meter.
A method described by Ficat and Arlet [9] was used to examine blood pressure in the femoral mar- row cavity. To perform the measurement, the anesthe- tized rats had their left femoral diaphysis exposed and a hole of d = 1.2 mm was drilled with a dentistic drill 1/3 of the distance from the proximal epiphysis.
A metal cannula was fixed tight in the hole. One end of the cannula was inserted in the marrow cavity where the osseous tissue contacted the marrow. The cannula was connected to the blood pressure measur- ing sensorvia a drain filled with 0.9% NaCl solution supplemented with heparin, which in turn was linked with the pressure meter.
Fifteen min was allowed after a rat had been con- nected to the set, in order to obtain stable parameters.
Following the recording of initial parameters, the ex- amined compounds were administerediv (as specified above). The right carotid vein had previously been prepared and the polyethylene cannula was inserted into it.
Tab. 1. Subgroups receiving adrenoceptor agonists and antagonists (in each main group)
Subgroup Adrenoceptor agonists and antagonists
1 n = 6 NE
10 µg/kg
NE 20 µg/kg
NE 40 µg/kg
PHT 1.5 mg/kg
NE 10 µg/kg
NE 20 µg/kg
NE 40 µg/kg
2 n = 6 NE
10 µg/kg
NE 20 µg/kg
NE 40 µg/kg
PR 1.5 mg/kg
NE 10 µg/kg
NE 20 µg/kg
NE 40 µg/kg
3 n = 6 E
10 µg/kg
E 20 µg/kg
E 40 µg/kg
PHT 1.5 mg/kg
E 10 µg/kg
E 20 µg/kg
E 40 µg/kg
4 n = 6 E
10 µg/kg
E 20 µg/kg
E 40 µg/kg
PR 1.5 mg/kg
E 10 µg/kg
E 20 µg/kg
E 40 µg/kg
5 n = 6 IP
3 µg/kg
IP 6 µg/kg
PR 1.5 mg/kg
IP 3 µg/kg
IP 6 µg/kg
NE norepinephrine, E epinephrine, IP isoprenaline, PHT phentolamine, PR propranolol
The examined parameters (mean blood pressure in the carotid artery and blood pressure in the femoral marrow cavity) were recorded continuously. The reading of the parameters to be determined was made using the recorder immediately following the admini- stration (0–0.25 min), and after the lapse of 0.5, 1, 2, 3, 5 and 10 min from the administration of catechola- mines.
The results are given in the tables as arithmetic mean values (± SEM) and as mean values of the dif- ferences between the initial value and the value ob- tained after the lapse of the mentioned time periods from catecholamine administration. Unpaired Stu- dent’s t-test was applied for statistical evaluation of the results.
Results
The mean blood pressure measured in the carotid ar- tery in the controls (C group) was 117.0 –119.0 mmHg, whereas the blood pressure in the femoral marrow cavity measured parallelly was 16.4–18.0 mmHg (Tabs 2, 5, 8).
The ovariectomized rats (OVX group) demon- strated a similar effect on the carotid artery blood pressure as in case of the controls. In case of the OVX group, the blood pressure in the marrow cavity was statistically significantly lower by about 40% when compared to the controls (Tabs 2, 5, 8).
The effect of norepinephrine on the arterial blood pressure and bone marrow cavity blood pressure in ovariectomized rats
The administration of NE to the controls at doses of 10, 20 or 40 µg/kg,iv increased blood pressure in the carotid artery by 41.71%, 75.21% and 85.13% of the initial value, respectively, when measured immedi- ately following the NE administration. Subsequently, the carotid artery blood pressure fell gradually and at 10 min following the NE administration, it reached the initial value. Simultaneously to the increase in ca- rotid artery blood pressure, the blood pressure in the femoral marrow cavity was also rising. Compared to the initial value, the increase was by 74.39% (at the dose of 10 µg/kg,iv), 101.22% (at the dose of 20 µg/kg, iv) and
121.95% (at the dose of 40 µg/kg,iv) (Tab. 2). Tab.2.Theeffectofnorepinephrine(NE)onthebloodpressureincontrolandovariectomizedrats GroupParameterInitial BP [mm Hg]
Difference(aftertheadministrationofNE)inrelationtotheinitialbloodpressure[mmHg] NE10µg/kgivNE20µg/kgivNE40µg/kgiv TimeaftertheadministrationofNE[min]TimeaftertheadministrationofNE[min]TimeaftertheadministrationofNE[min] 0–0.250.51235100–0.250.51235100–0.250.5123510 CA117.0 ±2.448.8 ±5.433.0 ±2.425.0 ±1.615.3 ±1.43.0 ±1.00.0 ±0.00.0 ±0.088.0 ±5.445.8 ±4.024.3 ±2.511.0 ±2.43.0 ±2.10.0 ±0.00.0 ±0.099.6 ±4.075.5 ±6.035.8 ±5.115.0 ±4.97.0 ±2.05.0 ±2.00.0 ±0.0 M16.4 ±0.212.2 ±1.09.8 ±1.06.8 ±0.62.8 ±0.20.0 ±0.00.0 ±0.00.0 ±0.016.6 ±0.612.4 ±0.66.0 ±0.43.8 ±0.40.2 ±0.20.0 ±0.00.0 ±0.020.0 ±1.08.0 ±0.44.8 ±1.01.0 ±0.5–0.2 ±0.20.0 ±0.00.0 ±0.0 OVXM10.0* ±0.514.0 ±1.010.0 ±0.28.8 ±0.43.0 ±0.40.2 ±0.20.0 ±0.00.0 ±0.020.8 ±2.014.7 ±0.48.2 ±0.44.0 ±0.50.2 ±0.20.0 ±0.00.0 ±0.028.8** ±1.218.4** ±1.210.2* ±0.43.3 ±0.42.0 ±0.51.0 ±0.10.0 ±0.0 C–controlrats,n=12;OVX–ovariectomizedrats,n=12.A–meanbloodpressureinthecarotidartery;M–bloodpressureinthemarrowcavity;InitialBP–bloodpressurebeforetheadministrationofNE. *p<0.05;**p<0.01–differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C)
NE administered at increasing doses of 10, 20 or 40 µg/kg,iv to the ovariectomized rats caused changes in carotid artery blood pressure similar to those ob- served in the controls. In relation to the initial value, the rise in marrow cavity blood pressure following NE administration was higher than in the controls, and immediately after such administration it equaled 140.00% (10 µg/kg), 208.00% (20 µg/kg) and 288.00% (40 µg/kg, p < 0.01) (Tab. 2).
The effect of phentolamine on the arterial blood pressure and bone marrow cavity blood
pressure in ovariectomized rats
The administration of phentolamine (PHT) to the con- trols resulted in a decreased blood pressure in the ca- rotid artery and marrow cavity (at 5 min after admini- stration by approximately 35% and 50%, respec- tively) (Tabs 3, 6). The administration of PHT in the ovariectomized group resulted in changes in blood pressure in the carotid artery and marrow cavity simi- lar to those observed in the controls.
The effect of norepinephrine on arterial blood pressure and marrow cavity blood pressure following phentolamine administration to the ovariectomized rats
PHT and subsequently NE at 10 µg/kg, iv adminis- tered to the controls did not influence blood pressure in the carotid artery or in the marrow cavity. The ad- ministration of NE at 20 µg/kg,iv after prior admini- stration of PHT to the controls resulted in a minor ca- rotid artery blood pressure increase, whereas the dose of 40 µg/kg, iv caused the pressure to increase by 18.75%. The administration of NE to the controls which had been administered PHT caused an increase in marrow cavity blood pressure by 15.56% (at the dose of 20 µg/kg, iv) and by 88.89% (at the dose of 40 µg/kg,iv) (Tab. 3).
PHT and subsequently NE, administered to the ovariectomized group elicited effects on blood pres- sure in the carotid artery similar to those observed in the controls. The administration of NE at the dose of 10 µg/kg, iv following PHT administration in the ovariectomized group, resulted in marrow cavity blood pressure changes similar to those observed in the controls, whereas the administration of NE at 20 or 40 µg/kg, iv to the same rats caused statistically signifi- cantly (p < 0.05) higher increases in the marrow cavity pressure when compared to the controls (Tab. 3).
The effect of propranolol on the blood pressure in the carotid artery and marrow cavity
in the ovariectomized rats
The controls displayed a drop in carotid artery blood pressure and a parallel drop of the pressure in the mar- row cavity following the administration of propra- nolol (PR). At 5 min after the administration, the arte- rial pressure fell by about 15%, while the marrow cavity pressure decreased by approximately 20%
when compared to the initial value (Tabs 4, 7, 9). PR administration to the ovariectomized rats caused a de- crease in the carotid artery and marrow cavity blood pressure similar to the controls.
The effect of norepinephrine on the blood pres- sure in the carotid artery and marrow cavity, following propranolol administration
to the ovariectomized rats
The administration of NE at 10, 20 or 40 µg/kg,iv fol- lowing PR administration resulted in the carotid ar- tery blood pressure increase by 10.00%, 30.0% and 50.00%, respectively. Parallelly to this increase, the administration of NE also caused an increase in blood pressure in the marrow cavity by 35.00% (10 µg/kg), 75.71% (20 µg/kg) and 107.14% (40 µg/kg) (Tab. 4).
The effect on blood pressure in the carotid artery in the ovariectomized rats administered NE following PR administration was similar to that observed in the controls.
The administration of PR followed by NE at 10 µg/kg,iv in the ovariectomized group, influenced the marrow cavity blood pressure similarly to the con- trols. The administration of NE at 20 or 40 µg/kg,iv to the same rats caused statistically significantly higher increases in the marrow cavity pressure than in case of the controls, by 158.95% (20 µg/kg, p < 0.05) and 271.58% (40 µg/kg, p < 0.01), respectively, in re- lation to the initial value (Tab. 4).
The effect of epinephrine on the arterial blood pressure and marrow cavity blood pressure in the ovariectomized rats
The administration of E to the controls at the dose of 10 µg/kg,iv resulted in blood pressure increase in the carotid artery by 46.34%. E administration at 20 or 40 µg/kg, iv resulted in an initial increase in carotid artery blood pressure by 67.73% and 84.25%, respec- tively, followed by a decrease by 8.68% (20 µg/kg)
Tab.3.Theeffectofnorepinephrine(NE)aftertheadministrationofphentolamine(PHT)onthebloodpressureincontrolandovariectomizedrats GroupParameterInitial BP/PHT [mm Hg]
Difference(aftertheadministrationofNE)inrelationtotheinitialbloodpressure[mmHg] NE10µg/kgivNE20µg/kgivNE40µg/kgiv TimeaftertheadministrationofNE[min]TimeaftertheadministrationofNE[min]TimeaftertheadministrationofNE[min] 0–0.250.51235100–0.250.51235100–0.250.5123510 CA80.0 ±3.80.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.06.5 ±2.61.0 ±3.80.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.015.0 ±3.09.0 ±2.05.0 ±2.13.5 ±2.11.0 ±1.00.0 ±0.00.0 ±0.0 M9.0 ±1.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.01.4 ±0.50.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.08.0 ±2.04.8 ±0.42.0 ±0.41.0 ±0.30.0 ±0.00.0 ±0.00.0 ±0.0 OVXM6.0 ±0.40.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.08.0* ±0.22.0 ±0.20.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.016.0* ±0.47.2 ±0.83.8 ±0.41.0 ±0.20.0 ±0.00.0 ±0.00.0 ±0.0 Ccontrolrats,n=6;OVXovariectomizedrats,n=6.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBP/PHTbloodpressureat5minaftertheadmini- strationofPTH.*p<0.05differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C) Tab.4.Theeffectofnorepinephrine(NE)aftertheadministrationofpropranolol(PR)onthebloodpressureincontrolandovariectomizedrats GroupParameterInitial BP/PR [mm Hg]
Difference(aftertheadministrationofNE)inrelationtotheinitialbloodpressure[mmHg] NE10µg/kgivNE20µg/kgivNE40µg/kgiv TimeaftertheadministrationofNE[min]TimeaftertheadministrationofNE[min]TimeaftertheadministrationofNE[min] 0–0.250.51235100–0.250.51235100–0.250.5123510 CA100.0 ±2.010.0 ±1.56.0 ±2.02.0 ±0.41.0 ±0.20.0 ±0.00.0 ±0.00.0 ±0.030.0 ±4.020.0 ±4.015.0 ±2.010.0 ±2.05.0 ±0.50.0 ±0.00.0 ±0.050.0 ±8.035.0 ±4.820.0 ±4.015.5 ±3.010.0 ±1.45.0 ±0.50.0 ±0.0 M14.0 ±2.05.0 ±1.04.0 ±1.23.0 ±0.21.5 ±0.20.0 ±0.00.0 ±0.00.0 ±0.010.6 ±2.08.0 ±2.45.2 ±1.03.0 ±1.00.2 ±0.20.0 ±0.00.0 ±0.015.0 ±2.210.0 ±0.85.4 ±0.62.2 ±0.2–0.4 ±0.10.0 ±0.00.0 ±0.0 OVXM9.5 ±0.68.0 ±1.47.0 ±1.04.5 ±1.02.0 ±0.50.0 ±0.00.0 ±0.00.0 ±0.015.1* ±0.210.0 ±2.06.5 ±0.54.0 ±0.20.0 ±0.00.0 ±0.00.0 ±0.025.8** ±0.415.0* ±0.410.0* ±0.56.5* ±0.2–0.5 ±0.10.0 ±0.00.0 ±0.0 Ccontrolrats,n=6;OVXovariectomizedrats,n=6.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBP/PRbloodpressureat5minaftertheadministra- tionofPR.*p<0.05;**p<0.01differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C)
and 10.53% (40 µg/kg). Simultaneously to the in- crease in carotid artery blood pressure, an increase in the marrow cavity pressure by 38.89% (10 µg/kg), 54.44% (20 µg/kg) and 55.56% (40 µg/kg) was re- corded. Subsequently, a drop in marrow cavity pres- sure was observed despite still elevated carotid artery pressure. The maximum drop in marrow cavity pres- sure was 11.11% (10 µg/kg), 13.89% (20 µg/kg) and 27.78% (40 µg/kg) (Tab. 5).
E administered at 10, 20 or 40 µg/kg, iv to rats of the ovariectomized group, elicited similar effects on the carotid artery blood pressure to those observed in the controls. E also had a biphasic effect on marrow cavity blood pressure in the ovariectomized rats, but the increase after the administration was statistically significantly higher than in the controls and immedi- ately after such administration it equaled 102.00%
(10 µg/kg, p < 0.05), 180.00% (20 µg/kg, p < 0.01) and 200.00% (40 µg/kg, p < 0.05). E administered to this group at 40 µg/kg also caused a statistically sig- nificantly (p < 0.05) higher decrease in marrow cavity blood pressure (in 2 min) when compared to the con- trols; the decrease equaled 80% of the initial value (Tab. 5).
The effect of epinephrine on the arterial blood pressure and marrow cavity blood pressure after administration of phentolamine to the ovariectomized rats
E at 10 µg/kg,iv administered to the controls after ad- ministration of PHT, did not demonstrate any influ- ence on blood pressure in the carotid artery or marrow cavity. The administration of E at 20 and 40 µg/kg,iv resulted in a rise in blood pressure in the carotid artery by 13.33% and 22.00%, respectively, immediately af- ter such administration. Parallel to the increase, a rise in marrow cavity blood pressure occurred by 18.75%
(20 µg) and 60.00% (40 µg) (Tab. 6).
The effects of E following PHT administration on blood pressure in the carotid artery in the ovariecto- mized rats were similar to those observed in the con- trols. E at 10 or 20 µg/kg, iv administered to the ovariectomized group after PHT, demonstrated a similar effect on the marrow cavity blood pressure as in the controls, whereas the administration of E at 40 µg/kg, iv to the same rats caused statistically sig- nificantly (p < 0.05) higher increase in the marrow cavity pressure when compared to the controls (Tab.
6). Tab.5.Theeffectofepinephrine(E)onthebloodpressureincontrolratsandovariectomizedrats GroupParameterInitial BP [mm Hg]
Difference(aftertheadministrationofE)inrelationtotheinitialbloodpressure[mmHg] E10µg/kgivE20µg/kgivE40µg/kgiv TimeaftertheadministrationofE[min]TimeaftertheadministrationofE[min]TimeaftertheadministrationofE[min] 0–0.250.51235100–0.250.51235100–0.250.5123510 CA118.7 ±5.755.0 ±5.034.0 ±4.515.0 ±2.54.0 ±0.5–1.5 ±1.0–1.0 ±0.50.0 ±0.080.4 ±3.468.0 ±4.030.0 ±2.0–0.2 ±0.2–10.3 ±2.0–6.0 ±2.00.0 ±0.0100.0 ±6.095.0 ±4.270.0 ±4.815.5 ±4.1–12.5 ±2.0–7.5 ±2.0–1.0 ±1.0 M18.0 ±0.87.0 ±0.23.0 ±0.50.0 ±0.0–2.0 ±0.4–1.2 ±0.80.0 ±0.00.0 ±0.09.8 ±0.64.0 ±1.0–1.0 ±0.4–1.0 ±0.2–2.5 ±1.0–1.6 ±0.40.0 ±0.010.0 ±1.08.0 ±1.04.4 ±1.5–5.0 ±1.0–3.0 ±0.20.0 ±0.00.0 ±0.0 OVXM10.0** ±0.410.2* ±0.86.0* ±0.53.0 ±0.0–2.4 ±1.0–1.0 ±0.2–0.4 ±0.2–0.2 ±0.218.0** ±0.410.0* ±0.46.4* ±0.2–1.0 ±0.2–3.2 ±0.2–1.0 ±0.20.0 ±0.020.0* ±0.415.0* ±0.610.0 ±1.0–8.0* ±0.8–6.6 ±1.0–3.4 ±1.00.0 ±0.0 Ccontrolrats,n=12;OVXovariectomizedrats,n=12.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBPbloodpressurebeforetheadministrationof E.*p<0.05;**p<0.01differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C)
Tab.6.Theeffectofepinephrine(E)aftertheadministrationofphentolamine(PHT)onthebloodpressureincontrolratsandovariectomizedrats GroupParameterInitial BP/PHT [mm Hg]
Difference(aftertheadministrationoFE)inrelationtotheinitialbloodpressure[mmHg] E10µg/kgivE20µg/kgivE40µg/kgiv TimeaftertheadministrationofE[min]TimeaftertheadministrationofE[min]TimeaftertheadministrationofE[min] 0–0.250.51235100–0.250.51235100–0.250.5123510 CA75.0 ±4.52.0 ±1.20.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.010.0 ±1.85.0 ±1.51.0 ±0.20.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.016.5 ±3.08.5 ±3.54.5 ±1.53.0 ±0.70.0 ±0.00.0 ±0.00.0 ±0.0 M8.0 ±1.20.3 ±0.30.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.01.5 ±0.50.8 ±0.20.4 ±0.30.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.04.8 ±0.44.2 ±1.23.2 ±1.01.6 ±0.41.2 ±0.60.0 ±0.00.0 ±0.0 OVXM5.0 ±1.00.5 ±0.50.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.03.0 ±0.21.0 ±0.50.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.09.2* ±0.28.0 ±0.45.0 ±0.52.0 ±0.21.0 ±0.20.0 ±0.00.0 ±0.0 Ccontrolrats,n=6;OVXovariectomizedrats,n=6.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBP/PHTbloodpressureat5minaftertheadmini- strationofPTH.*p<0.05differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C) Tab.7.Theeffectofepinephrine(E)aftertheadministrationofpropranolol(PR)onthebloodpressureincontrolratsandovariectomizedrats GroupParameterInitial BP/PR [mm Hg]
Difference(aftertheadministrationofE)inrelationtotheinitialbloodpressure[mmHg] E10µg/kgivE20µg/kgivE40µg/kgiv TimeaftertheadministrationofE[min]TimeaftertheadministrationofE[min]TimeaftertheadministrationofE[min] 0–0.250.51235100–0.250.51235100–0.250.5123510 CA102.0 ±2.050.0 ±1.230.0 ±1.014.5 ±3.06.0 ±3.00.0 ±0.00.0 ±0.00.0 ±0.069.0 ±3.559.0 ±2.523.0 ±7.014.0 ±1.85.0 ±1.03.0 ±1.00.5 ±1.580.5 ±3.666.5 ±2.055.0 ±3.325.0 ±2.010.5 ±1.57.0 ±1.00.0 ±0.0 M14.2 ±2.04.0 ±1.5–1.0 ±1.0–2.5 ±1.0–0.4 ±0.80.0 ±0.00.0 ±0.00.0 ±0.05.2 ±1.8–2.0 ±1.0–3.0 ±1.2–3.4 ±1.0–2.5 ±0.6–1.0 ±0.20.0 ±0.03.0 ±0.5–4.5 ±3.0–4.6 ±0.2–5.0 ±1.0–4.0 ±1.0–2.0 ±0.50.0 ±0.0 OVXM8.0 ±3.44.0 ±1.0–1.0 ±0.5–3.0 ±1.20.0 ±0.00.0 ±0.00.0 ±0.00.0 ±0.08.0 ±1.0–2.0 ±0.4–4.0 ±1.2–5.0 ±1.0–4.0 ±0.4–3.0 ±1.0–1.0 ±1.07.0* ±0.2–6.0 ±1.2–7.0* ±0.5–7.5 ±0.4–6.8 ±0.6–5.0 ±0.50.0 ±0.0 Ccontrolrats,n=6;OVXovariectomizedrats,n=6.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBP/PRbloodpressureat5minaftertheadministra- tionofPR.*p<0.05differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C)
The effect of epinephrine on the arterial blood pressure and marrow cavity blood pressure after prior administration of propranolol to the ovariectomized rats
The controls, which were administered E at 10, 20 or 40 µg/kg, iv after previous administration of PR, de- monstrated an increase in the carotid artery blood pressure by 49.02%, 67.65% and 78.92%, respec- tively. The examinations of E effect (given after pro- pranolol) on blood pressure in the marrow cavity demonstrated a short-term increase and a subsequent decrease in blood pressure. At 1 min after E admini- stration at 10 µg/kg,iv, the marrow cavity blood pres- sure dropped by 17.61%, and the doses of 20 µg/kg,iv or 40 µg/kg, iv resulted in a decrease in blood pres- sure by 23.94% and 35.21%, respectively (at 2 min after E administration) (Tab. 7).
E at 10 or 20 µg/kg,iv administered to the ovariec- tomized rats after PR, displayed changes in the ca- rotid artery and marrow cavity blood pressure similar to those observed in the controls. The administration of E at 40 µg/kg, iv following PR administration to the same rats caused statistically significantly (p < 0.05) higher in- crease (immediately following E administration) and sta- tistically significantly (p < 0.05) higher decrease (at 1 min after E administration) in the marrow cavity blood pres- sure when compared to the controls (Tab. 7).
The effect of isoprenaline on the blood pres- sure in the artery and marrow cavity
in the ovariectomized rats
IP given to the controls at 3 or 6 µg/kg,iv caused a de- crease in carotid artery blood pressure by 12.61% and 21.01%, respectively. Simultaneously to this decrease, also a drop in marrow cavity blood pressure by 16.67%
and 47.22%, respectively, occurred (Tab. 8).
IP administration to the ovariectomized rats elicited a drop in blood pressure in the carotid artery similar to the controls. The administration of IP at 6 µg/kg,iv to those rats resulted in a statistically significantly (p < 0.05) higher decrease in blood pressure in the marrow cavity when compared to the controls (Tab. 8).
The effect of isoprenaline on the arterial blood pressure and marrow cavity blood pressure af- ter prior administration of propranolol
to the ovariectomized rats
IP given at 3 or 6 µg/kg,iv to the controls which had been administered PR, did not evoke a hypotensive Tab.
8.Theeffectofisoprenaline(IP)onthebloodpressureincontrolratsandovariectomizedrats GroupParameterInitialBP [mmHg]Difference(aftertheadministrationofIP)inrelationtotheinitialbloodpressure[mmHg] IP3µg/kgivIP6µg/kgiv TimeaftertheadministrationofIP[min]TimeaftertheadministrationofIP[min] 0–0.250.51235100–0.250.5123510 CA119.0 ±4.0–15.0±3.0–5.0±2.5–1.5±0.50.0±0.00.0±0.00.0±0.00.0±0.0–25.0±3.5–20.5±4.4–14.0±4.0–8.0±2.0–5.0±2.2–2.0±1.50.0±0.0 M18.0 ±3.0–3.0±0.5–2.0±1.0–1.0±0.5–0.5±0.50.0±0.00.0±0.00.0±0.0–8.5±0.4–7.0±1.3–4.5±1.0–3.0±1.0–1.0±0.50.0±0.00.0±0.0 OVXM9.8* ±2.0–5.0±0.2–2.0±0.4–1.0±0.50.0±0.00.0±0.00.0±0.00.0±0.0–9.00*±0.5–10.0±1.0–6.0±0.6–4.0±1.0–2.0±0.5–1.0±0.50.0±0.0 Ccontrolrats,n=6;OVXovariectomizedrats,n=6.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBPbloodpressurebeforetheadministrationofIP. *p<0.05differencesstatisticallysignificantcomparedtotheresultsobtainedforcontrolrats(C)
effect and only a minor carotid artery blood pressure increase was observed. Also, blood pressure in the marrow cavity was not observed to fall (Tab. 9).
The administration of IP following PR administra- tion in the ovariectomized group resulted in carotid artery and marrow cavity blood pressure changes similar to those observed in the controls.
Discussion
The model of experimental bilateral ovariectomy- induced osteoporosis in rats, used in this study, may reflect disturbances characteristic of osteoporosis which develops in postmenopausal women as a result of stopped hormonal activity of the ovaries.
Earlier studies demonstrated that experimental ovariectomy-induced osteoporosis in rats was accom- panied by intensified resorption processes in bones and increased bone formation [17, 27]. Histomor- phometric measurements indicated that in the cortical bone on the side of periosteum, the bone formation process was intensified (an increased osteoid width and transverse growth of the bone), whereas on the side of marrow cavity, the process of resorption was intensified (increased marrow cavity transverse cross-section area and increased ratio of marrow cav- ity transverse cross-section area to tibial bone trans- verse cross-section area). Resorption process was also observed to be intensified in the trabecular bone [27].
The results showed the decreased mechanical properties of the bones and diminished mineral and calcium con- tent in the examined bones in ovariectomized rats [16].
The model of experimental osteoporosis induced by ovariectomy in rats was used in the present study to examine the effects of catecholamines on blood pressure in the femoral bone marrow cavity. In our study, the mean blood pressure in ovariectomized rats measured in the carotid artery approximated 118 mmHg and was not significantly different from the re- sults observed in the controls. Therefore, ovariectomy performed in rats did not allow us to induce hyperten- sion characteristic of menopausal women [5, 28]. The lack of the said hypertension in ovariectomized rats is additionally acknowledged by other reports [3, 10, 29]. Hemodynamic parameters in ovariectomized rats were scrutinized by Lam et al. [18]. They proved that ovariectomy did not significantly affect the systolic,
Tab.9.Theeffectofisoprenaline(IP)aftertheadministrationofpropranolol(PR)onthebloodpressureincontrolratsandovariectomizedrats GroupParameterInitial BP/PR [mmHg]
Difference(aftertheadministrationofIP)inrelationtotheinitialbloodpressure[mmHg] IP3µg/kgivIP6µg/kgiv TimeaftertheadministrationofIP[min]TimeaftertheadministrationofIP[min] 0–0.250.51235100–0.250.5123510 CA99.0±4.85.0±1.03.0±1.00.0±0.00.0±0.00.0±0.00.0±0.00.0±0.015.0±4.610.0±2.95.0±1.53.0±0.21.0±1.00.0±0.00.0±0.0 M13.0±2.02.0±0.51.0±0.50.5±0.20.0±0.00.0±0.00.0±0.00.0±0.03.0±0.22.2±1.01.5±0.51.0±0.51.0±0.20.0±0.00.0±0.0 Ccontrolrats,n=6;OVXovariectomizedrats,n=6.Ameanbloodpressureinthecarotidartery;Mbloodpressureinthemarrowcavity;InitialBP/PRbloodpressureat5minaftertheadministra- tionofPR
