Further study of possible direct vascular actions of indapamide in the conduit and renal arteriolar vessels of spontaneously hypertensive rats

The effect of indapamide on vascular reactivity and its properties as a calcium antagonist were studied in both isolated aorta and perfused renal vasculature of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Indapamide was given orally to SHR and WKY rats for 2 weeks at a dose of 5 mg/kg per day. During this peiod indapamide did not lower blood-pressure in SHR and WKY rats although there was an adequate concentration of indapamide in the blood. There were no differences observed in the vascular reactivity towards noradrenaline and high-K + in both the above mentioned vessels in either indapamide- or vehicle-pretreated SHR and WKY rats. Verapamil (10 −9-10 −5M) caused a concentration-dependent relaxation of high-K +-depolarized aortas and a decrease in the renal-arteriolar perfusion pressure elevated by high-K + in both strains of rat. However, indapamide (10 −7-10 −4M) did not affect the K +-induced effect on either vessel type. Preloading of the vessels in vivo with indapamide for 2 weeks did not influence the results. In conclusion, further evidence has been presented to show that indapamide does not have calcium-antagonist properties in conduit (aorta) or resistance (renal) vessels under hypertensive conditions. Preloading of the vessels with indapamide was not a prerequisite for the demonstration of a pharmacological action of indapamide.