Alpha 1-adrenoceptor subtypes mediating contraction of the femoral artery in spontaneously hypertensive rats.
alpha 1-Adrenoceptors (ARs) were divided into alpha 1H and alpha 1L subtypes by their different affinities for bunazosin or prazosin. alpha 1H-ARs were further subdivided into alpha 1A, alpha 1B, and alpha 1C subtypes. Therefore, this study was undertaken to determine which alpha 1-AR subtypes were involved in the activation of femoral artery preparations by alpha 1-AR agonists in spontaneously hypertensive rats (SHR). For comparison, aortic strips were also incorporated in the present study. In the presence of propranolol, deoxycorticosterone, and desipramine, norepinephrine (NE) contracted the vascular strips in a dose-dependent manner. Negative log EC50 values and maximum responses of NE-induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Sprague-Dawley and Wistar-Kyoto rats (WKY). Contractile responses of the SHR aortae to NE were similar to those of the normotensive tissues. Schild plot data for alpha 1-AR antagonists indicated that alpha 1-AR subtypes mediating contraction of the aorta were homogeneous and had high affinities for bunazosin (pA2 9.4, alpha 1H subtype) and WB 4101 (pA2 9.3) and a low affinity for 5-methylurapidil (pA2 7.7). In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were alpha 1H and alpha 1L subtypes. Bunazosin, at 10(-9) M, which could mask the alpha 1H subtype, yielded a Schild plot for bunazosin with a slope not different from unity and decreased the pA2 value for bunazosin (pA2 9.4 vs. 8.5).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Nagoya City University Medical School, Japan.
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Fujimoto
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D005263:Femoral Artery / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1