Increased Ca2+ sensitivity of alpha 1-adrenoceptor-stimulated contraction in SHR caudal artery.
Potassium and alpha-receptor-stimulated contractile responses of caudal artery rings of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were measured under conditions in which norepinephrine (NE) uptake and K+-induced NE release by nerve terminals were eliminated. The maximum isometric tension developed by SHR arterial rings was significantly more compared with WKY arterial rings when arteries were stimulated with NE but not when stimulated with K+. The Ca2+ sensitivity of NE-stimulated arterial rings was about twofold higher compared with WKY arterial rings. However, the Ca2+ sensitivity of K+-depolarized arterial rings was comparable between WKY and SHR. This increase in Ca2+ sensitivity was specifically due to changes in the alpha 1-receptor-mediated mechanisms in SHR. The 50% effective concentration (EC50) values for both NE and alpha 1-specific agonist, methoxamine hydrochloride, were comparable between WKY and SHR, suggesting that alpha 1-receptor sensitivity is not altered in SHR. The relative contributions of postsynaptic alpha 1- and alpha 2-receptors in caudal artery contractions as calculated from the experiments with alpha 1- and alpha 2-receptor agonist and antagonists were 80 and 20% in WKY and 95 and 5% in SHR, respectively. Nifedipine inhibition of caudal artery contractions was significantly greater (P less than 0.05) in SHR when stimulated with NE but not when stimulated with potassium. Our results indicate that the mechanisms involved in K+ depolarization-dependent contractions are not altered in SHR. However, the mechanisms involved in the coupling of alpha 1-adrenergic receptor and smooth muscle contractions may be altered in SHR caudal artery rings.
M B
MB
Aqel
R V
RV
Sharma
R C
RC
Bhalla
D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006973:Hypertension / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013268:Stimulation, Chemical; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
D007473:Ion Channels; D011942:Receptors, Adrenergic, alpha; D008729:Methoxamine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine