The purpose of this investigation is to determine the functional role of angiotensin II (AII) generated in the vasculature on systemic arterial pressure (BP), basal vascular tone and adrenergic reactivity. Stimuli responsible for the release of renin and AII from the intact vascular bed will be studied. Because of its highly reactive renin-angiotensin system and stable cardiovascular system during withdrawal of blood samples for the required assays, the rabbit will be utilized. Femoral artery perfusion pressure and BP will be monitored in pentobarbital anesthetized rabbits. A femoral venous shunt will allow for administration of captopril to the hindlimb without recirculating and thus allow for selective angiotensin converting enzyme inhibition. Nephrectomized and sham operated rabbits will be employed to compare the relative importance of AII formed in the hindlimb vasculature on basal parameters. In order to eliminate complications of nephrectomy on electrolyte balance and plasma urea and to further induce the influence of vasculature AII, the animals will undergo peritoneal dialysis before each experiment at 1, 2 and 4 days post op. Interventions to be studied on vascular renin and AII release will be beta 1 and beta 2-adrenoceptor stimulation, direct electrical stimulation of sympathetic nerves, hemorrhage, afferent nerve stimulation, changes in calcium and sodium and Goldblatt hypertension. The accompanying changes in BP, femoral vascular resistence and femoral vascular responses to adrengeric nerve stimulation and norepinehrine will be determined. Captopril and saralasin will be employed as a means of distinguishing the involvement of the vascular renin- angiotensin system during these intervetnions. Because of the postulated role of vascular AII in the regulation of BP and vascular tone in disease states such as hypertension and congestive heart failure and possibly under basal conditions, knowledge about this system is important.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL039698-01
Application #
3356534
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1988-03-01
Project End
1992-02-29
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Zimmerman, B G (2000) Greater blood pressure-lowering effect of the renin inhibitor EMD 58265 than an angiotensin-converting enzyme inhibitor in two-kidney one-clip Goldblatt rabbit. Clin Exp Pharmacol Physiol 27:370-7
Zimmerman, B G; Birt, P C (1997) Angiotensin II release from rabbit intrarenal arteries: a critical assessment. Am J Hypertens 10:306-14
Chen, K; Zhang, X; Dunham, E W et al. (1996) Kinin-mediated antihypertensive effect of captopril in deoxycorticosterone acetate-salt hypertension. Hypertension 27:85-9
Chen, K; Zimmerman, B G (1995) Angiotensin II-mediated renal vasoconstriction amenable to alpha 1-adrenoceptor blockade. Eur J Pharmacol 284:281-8
Zhang, X; Dunham, E W; Zimmerman, B G (1995) Threshold sodium excretory and renal blood flow effects of angiotensin converting enzyme inhibition. J Hypertens 13:1413-19
Birt, P C; Zimmerman, B G (1995) Intrarenal arterial network renin content and inhibition by EMD 58265. Am J Hypertens 8:433-6
Chen, K; Zimmerman, B G (1994) Comparison of renal hemodynamic effect of ramiprilat to captopril;possible role of kinins. J Pharmacol Exp Ther 270:491-7
Zimmerman, B G; Raich, P C (1992) Renal hemodynamics in canine DOCA-salt hypertension: effect of calcium channel blockade. Tohoku J Exp Med 166:147-54
Hajj-Ali, A F; Zimmerman, B G (1992) Enhanced blood pressure and renal hemodynamic effect of chronic versus acute lisinopril administration in the rabbit. J Pharmacol Exp Ther 263:158-62
Hajj-ali, A F; Zimmerman, B G (1992) Nitric oxide participation in renal hemodynamic effect of angiotensin converting enzyme inhibitor lisinopril. Eur J Pharmacol 212:279-81

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