Relaxing effects of adrenomedullin in rat mesenteric resistance arteries.
Exogenous adrenomedullin (ADM) is hypotensive in very small doses, through direct vasodilation of resistance arteries. In different region this is variably mediated by ADM and CGRP receptors. Mechanisms involve ADM effects upon smooth muscle to increase cAMP and to activate K+ channels, plus stimulation of endothelial NO release and inhibition of sympathetic noradrenaline release.


OBJECTIVE
We studied the mechanism of the vasodilator effect of ADM in vitro.


METHODS
Rat mesenteric resistance arteries (RMRA) in isometric conditions, were stimulated using four contracting agents: K+ 40 microM, phenylephrine 10 mM, PGF2alpha 10 microM, angiotensin II 1 microM. We used methylene blue 10 microM to examine the involvement of soluble guanylate cyclase (GC) in the relaxation induced by ADM.


RESULTS
We found that relaxation induced by ADM is endothelium-independent, similar regardless of the contracting agent (including high K+), and partially sensitive to methylene blue.


CONCLUSIONS
K+ channel activation by ADM is not essential for relaxation. Opposite to other authors, we suggest that ADM-induced vasodilation may involve endothelium-independent activation of soluble GC.
Serban
Ionela Lăcrămioara
IL
Gr. T. Popa University of Medicine and Pharmacy Iaşi, School of Medicine, Department of Physiology.
Serban
D N
DN
Haulică
I
I
D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D018015:Receptors, Calcitonin Gene-Related Peptide; D014665:Vasodilator Agents; D053607:Adrenomedullin; D006162:Guanylate Cyclase