Cholinergic vasodilatory effect of an imidazoindole on the nephrosclerosis of hypertensive rats

Pyridino [1,2-a] imidazo [5,4-b] indole (Compound 1) has been reported previously as an antihypertensive agent. Parenteral introductions of Compound 1 in spontaneously hypertensive rats (SHR) and in normotensive dogs have been found to reduce systolic blood pressure (SBP) in those animal models. Later studies have shown cholinomimetic effects of Compound 1 in animal tissue preparations and in live animals. Our experiments showed that daily oral administration of Compound 1 minimized the development of hypertensive nephrosclerosis and prevented premature death in male SHR. Compound 1 also potentiated cholinergic activity in isolated rabbit hearts. It is suggested that cholinergic vasodilation by Compound 1 is responsible for the hypotensive effect and prevention of nephrosclerosis in SHR.