Characterization of alpha-adrenoreceptor mediated reduction of flow in a saline-perfused constant pressure model of rat perfused hindquarters.
An analysis of vasopressor responses elicited by alpha-adrenoreceptor agonists and KCl in a constant pressure saline perfused model of rat perfused hindquarters is presented. Using methoxamine (alpha 1), cirazoline (alpha 1), B-HT 920 (alpha 2) and St 587 (alpha 1) as alpha-adrenoreceptor agonists, and rauwolscine and prazosin as selective alpha 2- and alpha 1-adrenoreceptor antagonists, respectively, it is concluded that alpha-adrenoreceptor mediated vasoconstriction in this model is mediated by the alpha 1-subtype. Pretreatment of the animals with reserpine (i.p., at various doses and dose-regimens) or addition of angiotensin II (10(-9)-10(-6) M), PGF2 alpha(10(-8) & 5 X 10(-7) M) or KCl (2 & 4 X 10(-3) M), or changing [Mg2+] did not significantly affect the potency or intrinsic activity of the alpha-adrenoreceptor agonists studied. Experiments with the calcium entry blocking drugs gallopamil and nifedipine, or deletion of CaCl2 from the perfusion solution, did not reveal a contribution from the influx of extracellular calcium towards alpha 1-adrenoreceptor-mediated reduction of flow in RPH. KCl-induced vasoconstriction in RPH was found to be sensitive to the blockade of calcium entry by calcium entry blocking drugs, but not to alpha-adrenoreceptor-blocking drugs and calmodulin antagonist. It is concluded that the model described here is of potential value in the characterization of alpha-adrenoreceptor antagonists and calcium entry blocking drugs under in vitro conditions in resistance vessels of the rat.
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015237:Dinoprost; D005711:Gallopamil / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011460:Prostaglandins F; D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; C030655:St 587; D005711:Gallopamil; D011189:Potassium Chloride; C024763:talipexole; D012110:Reserpine; D015237:Dinoprost; D003000:Clonidine; D002118:Calcium