Aim: To analyze the effects of endomorphins (EMs) and their analogs ([D-Pro2]EM-1, [D-Ala2]EM-1, [D-Pro2]EM-2 and [D-Ala2]EM-2) on the cardiovascular system of anestetized rats and to study its mechanism.
Methods: Responses to EMs and their analogs were investigated in the systemic vascular bed of rats and the mesenteric microarteria of Bufo gargarizans. Responses to EMs were investigated on the hindquarters of the rat vascular bed under constant-flow conditions and on the isolated rabbit thoracic aorta strips.
Results: The EMs and their analogs showed dose-related (10(-9)-10(-6) mol.L-1, i.v.) and naloxone-sensitive (2 mg.kg-1, i.v.) hypotension in mean arterial pressure of rats with similar duration and vasodilatation in mesenteric microarteria of Bufa gargarizans. The sequence of potencies was EMs > [D-Pro2] EM-2 > [D-Ala2]EM-2 > [D-Ala2]EM-1 > [D-Pro2]EM-1. EMs were shown not to relax the isolated rabbit thoracic aorta strips without endothelium. EMs, however, relaxed them with endothelium significantly. This action was blocked by Nx (10(-5) mol.L-1) and L-NNA (10(-4) mol.L-1).
Conclusion: The significant hypotensive activity of EMs and their analogs is mainly associated with their vasodilatation, which is related to the release of NO from vascular endothelium, and their potency is not completely related to their affinity for mu-opiate receptor.