title: Vasodilating actions of cromakalim in resting and contracting states of carotid arteries from spontaneously hypertensive rats.
abstract: To determine the properties of cromakalim-opened K+ channels in arterial smooth muscle of spontaneously hypertensive rats (SHR), the effects of cromakalim on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The addition of cromakalim or of nifedipine to resting strips caused a relaxation only in SHR. When strips from both strains were contracted with 15.9 mM K+, the magnitude of the precontraction was greater in SHR than in WKY. Under these conditions, relaxant responses to lower concentrations of cromakalim were decreased and those to higher concentrations of cromakalim were increased in SHR. When strips from both strains were contracted with a different concentration of K+ to an equivalent magnitude (78% of the maximum) relaxant responses to cromakalim were greater in SHR than in WKY. When strips were contracted with 10(-7) M norepinephrine, the precontraction was similar between SHR and WKY, and relaxant responses to cromakalim were greater in SHR. In both strains, the relaxant responses to cromakalim were competitively antagonized by glibenclamide, a blocker of ATP-sensitive K+ (KATP) channels, with a pA2 value of approximately 7.3. Charybdotoxin (10(-7) M), a blocker of Ca(2+)-activated K+ (KCa) channels, did not inhibit the relaxant responses to cromakalim in both strains. Charybdotoxin alone elicited a contraction, which was greater in SHR than in WKY. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was higher in SHR than in WKY. The addition of cromakalim (10(-5) M) to the resting strips increased the 86Rb efflux rate constant in both strains to a similar peak value. The addition of nifedipine (10(-7) M) to the resting strips decreased the basal 86Rb efflux rate constant only in SHR, and concomitantly affected the action of cromakalim in SHR. The results suggest that (1) cromakalim caused arterial relaxation via the opening of KATP channels in both SHR and WKY, (2) although the relaxant effects of cromakalim tended to be greater in SHR than in WKY, the differences were rather small, depended on the precontraction tone and varied with the concentration of the vasoconstrictors, and (3) there was an increased basal Ca2+ influx and a high activation of KCa channels in the resting state of SHR arteries, and these changes might influence the effects of cromakalim.
authors.affiliation: Department of Pharmacology, Nagoya City University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: K
authors.initials: K
authors.lastname: Masuzawa-Ito
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects; D018999:Charybdotoxin; D019806:Cromakalim; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology; D013045:Species Specificity; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D011758:Pyrroles; D012604:Scorpion Venoms; D014665:Vasodilator Agents; D019806:Cromakalim; D018999:Charybdotoxin; D011188:Potassium; D005905:Glyburide; D009638:Norepinephrine