Effects of endothelial impairment by saponin on the responses to vasodilators and nitrergic nerve stimulation in isolated canine corpus cavernosum

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Abstract
Responsiveness to EDRF‐releasing substances and inhibitory nerve stimulation of canine isolated penile corpus cavernosum with and without saponin treatment were investigated. Histological studies demonstrated that saponin did not detach endothelial cells from underlying tissues, but induced degenerative changes in the endothelial cells selectively. In the cavernous strips contracted with phenylephrine, addition of acetylcholine, sodium nitroprusside, ATP and Ca2+ ionophore A23187 induced relaxations, but substance P and bradykinin did not change the muscle tone. Acetylcholine‐induced relaxation was significantly attenuated but not abolished by NG‐nitro‐L‐arginine (L‐NOARG). L‐arginine restored the response inhibited by L‐NOARG. The L‐NOARG resistant relaxation was not influenced by 1H[1,2,4]oxadiazole[4,3‐a]quinoxalin‐1‐one (ODQ) but was suppressed in the strips contracted with K+. Treatment with saponin abolished the relaxation elicited by acetylcholine and A23187 but did not influence the response to nitroprusside and ATP. The ATP‐induced relaxation was attenuated by aminophylline. Transmural electrical stimulation at 2–20 Hz produced endothelium‐independent relaxations which were abolished by tetrodotoxin and L‐NOARG but unaffected by treatment with saponin. In saponin‐treated cavernous strips, the neurogenic relaxation was not affected by acetylcholine, physostigmine, atropine and vasoactive intestinal peptide (VIP) but was abolished by ODQ. It is concluded that acetylcholine‐induced relaxations are endothelium‐dependent and mediated partly by NO and also by other substances from the endothelium. The endothelium‐independent relaxation to ATP is likely to be mediated by P1 purinoceptors. The function of nitrergic nerve does not seem to be prejunctionally modulated by acetylcholine and VIP. British Journal of Pharmacology (1999) 127, 802–808; doi:10.1038/sj.bjp.0702623