title: Augmented contributions of voltage-gated Ca2+ channels to contractile responses in spontaneously hypertensive rat mesenteric arteries.
abstract: The observation that organic Ca2+ channel blockers are more effective in lowering blood pressure and peripheral resistance in hypertensive compared to normotensive subjects suggests that there is a greater contribution from voltage-gated Ca2+ channels (CaL) to vascular force maintenance in hypertensive arteries. This study tests this hypothesis by comparing the effects of Bay k 8644 and nisoldipine on basal force development, contractile responses to norepinephrine and serotonin, and Ca2+ currents (ICa) in mesenteric artery (MA) from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). MA rings were used to record isometric contractions at Lmax. Single cells were isolated by collagenase plus elastase for measurement of CaL properties by patch-clamp methods. Contractile responses to Bay k 8644 were larger and more sensitive in SHR than WKY, and were larger in endothelium-denuded compared to intact rings. In SHR, the addition of 10 nmol/L Bay k 8644 increased contractile sensitivity to norepinephrine (NE) and serotonin (5HT), and increased maximum response to 5HT. In WKY, 10 nmol/L Bay k 8644 produced a small increase in 5HT sensitivity with no effect on maximum response, and had no effect on NE responses. In the presence of 1 mumol/L nisoldipine, the maximum response and the sensitivity to both NE and 5HT were decreased in both WKY and SHR with the inhibitory effects of nisoldipine being larger in SHR than WKY. Peak ICa was larger in SHR, and current-voltage curves were shifted toward more negative voltages compared to WKY. Bay k 8644 increased ICa in both WKY and SHR myocytes with no apparent difference in the magnitude of its effect when expressed as a percent of control ICa. These results suggest that CaL contribute significantly to tonic force maintenance as well as to agonist responses in MA from both WKY and SHR, but with a much larger contribution in SHR. Differences in the sensitivity of CaL to Bay k 8644 were not responsible for the differences in contractile responses to this agonist.
authors.affiliation: Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146, USA.
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: I
authors.initials: I
authors.lastname: Lozinskaya
authors.forename: R H
authors.initials: RH
authors.lastname: Cox
mesh_terms: D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014662:Vasoconstrictor Agents; D012701:Serotonin; D009638:Norepinephrine