Involvement of maxi-K(Ca) channel activation in atrial natriuretic peptide-induced vasorelaxation.
Large conductance, voltage- and Ca2+-sensitive K+ (maxi-K(Ca)) channels play an important role in the regulation of vascular smooth muscle excitability and contractility. The activity of maxi-K(Ca) channels is modified by a variety of intracellular messengers including cGMP, as well as by voltage and Ca2+. In the present study, we investigated the functional relevance of maxi-K(Ca) channels in atrial natriuretic peptide (ANP)-mediated vasorelaxation in the isolated rat mesenteric artery. ANP produced concentration-dependent relaxation in the de-endothelialized rat mesenteric artery. Iberiotoxin, a specific blocker of maxi-K(Ca) channels, greatly attenuated the ANP-induced vasorelaxation. Similarly, a large portion of the vascular relaxation induced by 8-Bromo-cGMP, a membrane permeable analogue of cGMP, was inhibited by iberiotoxin. These results indicate that activation of maxi-K(Ca) channels contributes substantially to the vascular relaxation produced by ANP in the rat mesenteric artery. Intracellular cGMP, increased by ANP, and the subsequent activation of cGMP-dependent protein kinase (PKG) may play a central role in the activation of maxi-K(Ca) channels in the ANP-produced vascular relaxation.
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Y
Y
Tanaka
M
M
Aida
H
H
Tanaka
K
K
Shigenobu
L
L
Toro
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D015221:Potassium Channels; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D015237:Dinoprost; D006152:Cyclic GMP; D002118:Calcium