Elcatonin-mediated contractile and relaxant responses in SHR femoral artery
Abstract
Aim: To study the effect of repeated systemic injections of elcatonin (a synthetic analog of eel calcitonin) on the responses of rat femoral artery preparation to vasoactive drugs and to determine subtypes of muscarinic cholinoceptors involved in acetylcholine (ACh)-induced vasorelaxation in elcatonin-treated rats.
Methods: Spontaneously hypertensive rats (SHR) were treated sc with elcatonin, 0.5 and 5 U/kg, 3 times a week for 2 weeks. Responses to vasoactive drugs were determined in helically cut strips of femoral arteries of these rats. Schild plot data for muscarinic cholinoceptor antagonists were obtained on these vascular strips, using ACh as an agonist.
Results: Elcatonin did not alter systemic blood pressure and contractile responses of the femoral artery to KCl, norepinephrine, 5-hydroxytryptamine, and prostaglandin F(2alpha). Elcatonin attenuated isoproterenol-induced relaxation, increased ACh- and ATP-induced relaxations, and did not change relaxant responses to sodium nitroprusside and cromakalim in the femoral artery. Nitro L-arginine in the combination with tetraethylammonium (or charybdotoxin) completely abolished the relaxant response to ACh in the control but not in the elcatonin-treated arteries. The muscarinic cholinoceptor subtype involved in the ACh-induced relaxation was M3 in the elcatonin-treated as well as control SHR.
Conclusion: Elcatonin decreases beta-adrenoceptor-mediated relaxation and increases M(3) cholinoceptor-mediated relaxation in the SHR femoral artery. Although the ACh-induced relaxation is explained by stimulated releases of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the SHR artery, a NO-and EDHF-independent mechanism in addition to NO and EDHF is responsible for the response to ACh in the femoral artery from the elcatonin-treated SHR.
Keywords:
Methods: Spontaneously hypertensive rats (SHR) were treated sc with elcatonin, 0.5 and 5 U/kg, 3 times a week for 2 weeks. Responses to vasoactive drugs were determined in helically cut strips of femoral arteries of these rats. Schild plot data for muscarinic cholinoceptor antagonists were obtained on these vascular strips, using ACh as an agonist.
Results: Elcatonin did not alter systemic blood pressure and contractile responses of the femoral artery to KCl, norepinephrine, 5-hydroxytryptamine, and prostaglandin F(2alpha). Elcatonin attenuated isoproterenol-induced relaxation, increased ACh- and ATP-induced relaxations, and did not change relaxant responses to sodium nitroprusside and cromakalim in the femoral artery. Nitro L-arginine in the combination with tetraethylammonium (or charybdotoxin) completely abolished the relaxant response to ACh in the control but not in the elcatonin-treated arteries. The muscarinic cholinoceptor subtype involved in the ACh-induced relaxation was M3 in the elcatonin-treated as well as control SHR.
Conclusion: Elcatonin decreases beta-adrenoceptor-mediated relaxation and increases M(3) cholinoceptor-mediated relaxation in the SHR femoral artery. Although the ACh-induced relaxation is explained by stimulated releases of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the SHR artery, a NO-and EDHF-independent mechanism in addition to NO and EDHF is responsible for the response to ACh in the femoral artery from the elcatonin-treated SHR.