Effects of 6-iodo-amiloride, a sodium channel blocker, on cardiovascular parameters in spontaneously hypertensive and Wistar-Kyoto rats.

6-Iodo-amiloride, an analogue of the sodium channel blocker amiloride, was infused intravenously for 10 min in anaesthetized Okamoto spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats in doses ranging from 0.08 to 0.38 mg/100 g body weight. Systemic arterial blood pressure and urine flow were measured for 120 min. In SHR, 6-iodo-amiloride produced a prompt, sustained, dose-dependent decrease in pressure. The lower doses were associated with increased urine flow and sodium excretion, while higher doses were not. Paradoxically, in WKY all doses produced a small dose-independent sustained increase in pressure and were associated with diuresis and natriuresis. 6-Iodo-amiloride had no effect on cardiac output, dP/dt or heart rate in isolated working hearts from SHR or WKY. However, addition of 6-iodo-amiloride to physiological salt solution bathing an isolated Wistar rat tail artery produced hyperpolarization of impaled vascular smooth muscle cells. These studies show that 6-iodo-amiloride is a vasodilatory antihypertensive agent in SHR, and that this can be associated with natriuresis and diuresis.