The relationship between the elevated blood pressure of the spontaneously hypertensive rat and the chemical sensitivity of smooth muscle to adrenergic agents.
The mean arterial blood pressure (MAP) and the sensitivity of a variety of isolated smooth muscle preparations to noradrenaline were determined in spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) rats, and a number of genetically related animals obtained by cross-breeding SHR and WKY (F1, F2, and F3; and "backcrossed" strains BC1(S) and BC1(W) ). The major objective of this study was to determine whether there was a clear relationship between the postsynaptic sensitivity of smooth muscle to noradrenaline and the blood pressure of the animal and, in addition, determine how neuronal uptake1 activity could modify postsynaptic sensitivity. The mean arterial blood pressure profile of the animals studied was for the 6- to 8-week animals: SHR greater than F1 greater than WKY; for the 12- to 16-week group: SHR = BC1(S) greater than F1 greater than BC1(W) greater than WKY; and for the greater than 52 week group: SHR greater than BC1(S) = F1 greater than BC1(W) greater than WKY [F1 obtained from SHR X WKY; BC1(S) = SHR X F1; BC1(W) = WKY X F1]. With the exception of the aorta from F1 animals, the noradrenaline mean effective dose (ED50) recorded from thoracic aortae, tail artery, portal vein, and anococcygeus tissues were not significantly different. After a 20-min pretreatment of tissues from 12- to 16-week rats (but not from 6- to 8-week rats) with 4 X 10(-5) M cocaine, there was a significantly greater leftward shift, as indicated by the noradrenaline ED50 before: noradrenaline ED50 after cocaine ratio, in the tail artery preparation from the SHR compared with the WKY; however, no significant differences in the ED50 ratios were noted for the thoracic aorta, the portal vein, or the anococcygeus tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D003042:Cocaine; D009638:Norepinephrine