Vasomotor action of insulin on the rabbit normal cavernous smooth muscle

Investigations on the effects of insulin on the normal vasculature have produced conflicting results. This study was aimed at establishing the vasomotor actions of insulin on normal cavernous smooth muscle. Insulin produced dose-dependent (10(-10)-10(-5) M) relaxation of the norepinephrine-precontracted strips of cavernosum, and of Bay K8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-2(trifluoromethylphenyl)pyridine-5-carboxylate]-precontracted strips. Endothelial denudation or indomethacin (10 microM) pre-treatment significantly reduced these insulin-induced relaxations, whereas NG-nitro-L-arginine methyl ester (L-NAME, 5 mM) did not. Moreover, the pre-treatment of the cavernosum strips with a prostacyclin synthesis inhibitor [9,11-diazo-15-deoxy-prostaglandin H2 (U-51605), 10 microM] significantly reduced insulin-induced response, whereas pretreatment with a cyclooxygenase-2 (COX-2) inhibitor (NS-398, 10 microM) did not. In addition, responses to insulin were not inhibited by K+ channel blockers, i.e., tetraethylammonium (TEA, 10 mM) or 4-aminopyridine (4-AP, 10 microM). Moreover, L-type Ca2+ currents were reduced by prostacyclin (2 microM) but not by insulin (10 microM). We conclude that insulin induces the endothelium-dependent relaxation of cavernous smooth muscles and that this relaxation response may emanate from the direct inhibition of L-type Ca2+ channels by prostacyclin.