Abstract
The blood pressure, renal function, baroreflex response of heart rate and noradrenaline (norepinephrine) pressor response were determined in conscious, normotensive, sodium-replete dogs that had received fosinopril. Oral administration of fosinopril at a dose of 1 mg/kg per day for 5 days decreased the systolic arterial pressure from 147.1±3 to 131.8±4.3 mmHg (p<0.05) and the mean arterial pressure from 99.7±3.9 to 87.5±2.8 mmHg (p<0.05), while heart rate was unchanged. A study of the noradrenaline pressor response showed a tendency to alleviate the increased MAP by fosinopril treatment, although this was not significant. There were no significant changes in the sensitivity of the baroreflex response in HR, although the setpoint was reduced. After 7 days of fosinopril treatment, the glomerular filtration rate had increased by 18.5% (p<0.05). The effective renal plasma flow tended to increase, leaving the filtration fraction unchanged. The renal vascular resistance was reduced by 11.3% (p<0.05). Fosinopril caused a significant 41.5% increase in urinary excretion of Na+ (p<0.05), along with an elevation of urinary excretion of K+ and Cl–. It is concluded that fosinopril can lower the blood pressure, reduce the noradrenaline pressor response and lower the cardiac baroreflex setpoint to noradrenaline. Oral administration of fosinopril for 7 days affects both the renal haemodynamics and electrolyte excretions in conscious, normotensive, sodium-replete dogs.
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REFERENCES
Asaad, M.M. and Antonaccio, M.J., 1982. Vascular wall renin in spontaneously hypertensive rats: potential relevance to hypertension maintenance and antihypertensive effect of captopril. Hypertension, 4, 487-493
Bovée, K.C., 1984. Canine Nephrology, (Harwal Publishing Co., Media, PA, USA), 78
Bovée, K.C., Wong, P.C., Timmermans, P.B.M.W.M. annd Thoolen, M.J.M.C., 1991. Effects of nonpeptide angiotensin II receptor antagonist DuP753 on blood pressure and renal functions in spontaneously hypertensive PH dogs. American Journal of Hypertension, 4, 327S-333S
Brun, C., 1951. A rapid method for the determination of para-aminohippuric acid in kidney function tests. Journal of Laboratory and Clinical Medicine, 37, 955-958
Brunner, H.R., Kirshman, J.D., Sealey, J.E. and Laragh, J.H., 1971. Hypertension of renal origin: evidence for two different mechanisms. Science, 174, 1344-1346
Bumpus, F.M., Sen, S., Smeby, R.R., Sweet, C., Ferrario, C.M. and Khosla, M.C., 1973. Use of angiotensin II antagonists in experimental hypertension. Circulation Research, 32(supplement), I150-I158
Clappison, B.H., Anderson, W.P. and Johnston, C.L., 1981. Renal hemodynamics and renal kinins after angiotensin converting enzyme inhibitor. Kidney International, 20, 615-620
Clough, D.P., Collis, M.G., Conway, J., Hatton, R. and Keddie, J.R., 1982. Interaction of angiotensin converting enzyme inhibitors with the function of the sympathetic nervous system. American Journal of Cardiology, 49, 1410-1414
DeForrest, J.M., Waldron, T.L. and Antanaccio, M.J., 1982. Renal response to captopril in conscious dogs pretreated with indomethacin. American Journal of Physiology, 243, F543-F548
DeForrest, J.M., Waldron, T.L., Harvey, C., Scalese, B., Rubin, B., Powell, J.R., Petrillo, E.W. and Cushman, D.W., 1989. Fosinopril, a phosphinic acid inhibitor of angiotensin I converting enzyme: in vitro and pre-clinical in vivo pharmacology. Journal of Cardiovascular Pharmacology, 14, 730-736
DeForrest, J.M., Waldron, T.L., Harvey, C., Scalese, B., Mitch, S., Powell, J.R., Petrillo, E.W. and Cushman, D.W., 1990. Blood pressure lowering and renal hemodynamic effects of fosinopril in conscious animal models. Journal of Cardiovascular Pharmacology, 16, 139-146
Faria, F.A.C. and Salgado, M.C.O., 1992. Facilitation of noradrenergic transmission by angiotensin in hypertensive rats. Hypertension, 19(supplement II), II30-II35
Fernandez, M., Madero, R., Gonzales, D., Camacho, P., Villalpando, J. and Arriaga, J., 1994. Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients. Hypertension, 23(supplement I), I207-I210
Hamlin, R.L. and Nakayama, T., 1998. Comparison of some pharmacokinetic parameters of 5 angiotensin-converting enzyme inhibitors in normal beagles. Journal of Veterinary Internal Medicine, 12, 93-95
Hoyer, J., Schulte, K.L. and Lenz, T., 1993. Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure. Clinical Pharmacokinetics, 24, 230-254
Ichikawa, S., Johnson, J.A., Fowler, W.L. Jr., Payne, C.G., Kurz, K. and Keitzer, W.F., 1978. Pressor responses to norepinephrine in rabbits with 3 days and 30 days renal artery stenosis: the role of angiotensin II. Circulation Research, 43, 437-446
Kelly, J.G. and O'Malley, K., 1990. Clinical pharmacokinetics of the newer ACE inhibitors: a review. Clinical Pharmacokinetics, 19, 177-196
Kimbrough, H.M., Vaughan, D., Carey, R.M. and Ayers, C.R., 1977. Effect of intrarenal angiotensin II blockade on renal function in conscious dogs. Circulation Research, 40, 174-178
Lee, W.B. and Lumbers, E.R., 1981. Angiotensin and the cardiac baroreflex response to phenylephrine. Clinical and Experimental Pharmacology and Physiology, 8, 109-117
Mitchell, H.C., Smith, R.D., Cutler, R.E., Sica, D., Videen, J., Thompsen-Bell, S., Jones, K., Bardley-Guidry, C. and Toto, R.D., 1997. Racial differences in the renal response to blood pressure lowering during chronic angiotensin-converting enzyme inhibitor: a prospective double blind randomized comparison of fosinopril and lisinopril in older hypertensive patients with chronic renal insufficiency. American Journal of Kidney Diseases, 29, 897-906
Mundoch, D. and McTavish, D., 1992. Fosinopril: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in essential hypertension. Drugs, 43, 123-140
Oren, S., Messerli, F.H., Grossman, E., Garavaglia, G.E. and Frohlich, E.D., 1991. Immediate and short-term cardiovascular effects of fosinopril, a new angiotensin-converting enzyme inhibitor, in patients with essential hypertension. Journal of the American College of Cardiology, 17, 1183-1187
Potter, E.K. and Reid, I.A., 1985. Intravertebral angiotensin II inhibits cardiac vagal efferent activity in dogs. Neuroendocrinology, 40, 493-496
Reid, I.A. and Chou, L., 1990. Analysis of the action of angiotensin II on the baroreflex control of heart rate in conscious rabbits. Endocrinology, 126, 2749-2756
Rizzoni, D., Castellaro, M., Porteri, E., Bettoni, G., Muiesan, M.L., Cinelli, A. and Rosei, A., 1995. Effects of low and high doses of fosinopril on the structure and function of resistance arteries. Hypertension, 26, 118-123
Sokabe, H., 1966. Renin activity of the kidney in the spontaneously hypertensive rat. Japanese Journal of Physiology, 16, 380-388
Sweet, C.S., Gaul, S.L., Reitz, P.M., Blaine, E.H. and Ribeiro, L.T., 1983. Mechanisms of action of enalapril in experimental hypertension and acute left ventricular failure. Journal of Hypertension, 1(supplement 1), 53-63
Weber, M.A., 1992. Fosinopril: a new generation of angiotensin-converting enzyme inhibitors. Journal of Cardiovascular Pharmacology, 20(supplement 10), S7-S12
Young, M.K. Jr. and Raisz, L.G., 1952. An anthrone procedure for determination of inulin in biological fluids. Proceedings of the Society for Experimental Biological Medicine, 80, 771-774
Zimmerman, B.G., 1973. Blockade of adrenergic potentiation effect of angiotensin by 1-sar-8-ala-angiotensin II. Journal of Pharmacology and Experimental Therapeutics, 185, 486-592
Zimmerman, B.G., 1981. Adrenergic facilitation by angiotensin: does it serve a phsyiological function? Clinical Science, 60, 343-348
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Buranakarl, C., Kijtawornrat, A. & Nampimoon, P. Effects of Fosinopril on Renal Function, Baroreflex Response and Noradrenaline Pressor Response in Conscious Normotensive Dogs. Vet Res Commun 25, 355–366 (2001). https://doi.org/10.1023/A:1010638609216
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DOI: https://doi.org/10.1023/A:1010638609216