Chronic Administration of Tiapamil Prevents Hemodynamic Alterations Accompanying Development of High Blood Pressure in Hypertensive Rats

Abstract

Daily oral administration of tiapamil (2 X 50-2 X 150 mg/kg, for 13 weeks) to spontaneously hypertensive rats (SHR) resulted in a dose-dependent inhibition of hypertension development, with complete prevention occurring at the highest dose. Tiapamil (2 X 100 mg/kg/day, p.o.) also prevented development of high blood pressure in deoxycorticosterone acetate-NaCl hypertensive rats (DOCA). A comparative hemodynamic analysis was carried out on age-matched (17-week-old) control SHR, tiapamil-treated (2 X 150 mg/kg/day, p.o.) SHR, and normotensive Wistar-Kyoto rats (WKY). Tiapamil-treated SHR and WKY had a significantly lower mean arterial pressure and total peripheral resistance as well as a higher cardiac output than untreated SHR. Vasoconstrictor responses to norepinephrine as well as to angiotensin I and II were significantly lower in tiapamil-treated than in untreated SHR. By contrast, isoproterenol elicited a fall in blood pressure in all three groups, the extent of which correlated directly with the magnitude of basal blood pressure levels. Tiapamil also caused a concentration-dependent depression of depolarization-induced vasoconstrictor responses in isolated mesenteric and renal arteries from SHR. The results of this study indicate that chronic administration of tiapamil will prevent the development of hypertension in SHR and DOCA rats as well as protect against accompanying hemodynamic alterations. This inhibitory effect on blood vessels that maintain peripheral resistance at elevated levels is a consequence of the vascular-selective calcium entry blocking properties of tiapamil.