Receptor-specific influence of endothelin-1 in the erectile response of the rat

Specific receptor antagonists were used to examine the role of endothelin-1 (ET-1) in the erectile response of the rat. In these studies, intact rats were cannulated to permit the continuous recording of mean arterial pressur e (MAP) and intracavernosal pressure (CCP). Erection was induced by electri cal stimulation of the autonomic ganglion, which regulates blood flow to th e penis. The animals were subjected to intracavernosal injection with vehic le only (Cont) or with an antagonist to the endothelin-A receptor (ETA) or to the endothelin-B receptor (ETB). Blockade of the ETA or the ETB had no e ffect on the erectile response (CCP/MAP) during maximal ganglionic stimulat ion. When ET-1 was injected into Cont rats, there was a marked vasoconstric tion with a sharp rise in MAP and a decline in CCP as the cavernosal arteri oles constricted and limited inflow. The injection of the ETA antagonist pr evented the vasoconstriction after ET-1 injection into Cont rats, whereas b lockade of the ETB had no effect on the vasoconstrictive effect to ET-1. Si milar results were obtained during submaximal ganglionic stimulation. With minimal levels of ganglionic stimulation, ET-1 injection led to a moderated degree of vasodilation in the presence of the ETA antagonist. The ETB anta gonist failed to alter the CCP response during minimal stimulation, but it did have a marked effect on the MAP response to ET-1 injection. The results of these studies confirm that cavernosal tissue of the rat penis is highly responsive to ET-1. However, the failure of the ET-1 antagonists to affect penile erection in response to ganglionic stimulation reflects a minimal r ole of ET-1 in the erectile response in the rat.