Mechanisms of vasodilation induced by vasoactive intestinal polypeptide in rabbit mesenteric artery.
Vasoactive intestinal polypeptide (VIP; over 10(-13) M) inhibited the norepinephrine (NE)-induced contraction evoked from the rabbit mesenteric artery. Increased concentrations of VIP (over 10(-9) M) inhibited the contractions induced by caffeine and 39 mM [K]o. However, VIP (below 10(-7) M) had no effect on the membrane potential and resistance of muscle cells. In Ca-free solution, VIP (10(-10) M) inhibited the NE-induced contraction, but the second application of NE after removal of VIP enlarged the amplitude of contraction over that in the control. Yet when 10(-9) M VIP was applied, both the first and second contractions were consistently smaller than those observed by application of 10(-10) M VIP. In Na- and Ca-free solution, repetitive applications of NE generated contractions longer than those observed in Ca-free solution. When VIP (10(-10) M) was applied once (3 min), the contraction was inhibited only once during repetitive applications of NE. VIP (over 10(-9) M) dose dependently inhibited the NE-induced contraction and had a long-lasting inhibition after washout of the tissue. In saponin-treated skinned muscles, VIP (10(-7) M) had no effect on the Ca-induced contraction or on the Ca store sites. VIP (over 10(-8) M) was about 10 times more potent than equimolar concentrations of isoproterenol in increasing the content of adenosine 3', 5'-cyclic monophosphate (cAMP). These results indicate that VIP (10(-10) M) selectively inhibits the Ca release activated by NE, and high concentrations (over 10(-9) M) would expectedly increase the Ca extrusion from cells following increase in the levels of cAMP.
Itoh
T
T
Sasaguri
T
T
Makita
Y
Y
Kanmura
Y
Y
Kuriyama
H
H
D000818:Animals; D002110:Caffeine / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D012503:Saponins; D014660:Vasoactive Intestinal Peptide; D002110:Caffeine; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine