The relationship between the elevated blood pressure of the spontaneously hypertensive rat and the chemical sensitivity of smooth muscle to adrenergic agents

Abstract

The mean arterial blood pressure (MAP) and the sensitivity of a variety of isolated smooth muscle preparations to noradrenaline [norepinephrine] 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 uptake activity could modify postsynaptic sensitivity. The mean arterial blood pressure profile of the animals studied was for the 6-8 wk animals: SHR > F1 > WKY; for the 12-16 wk group: SHR = BC1(S) > F1 > BC1(W) > WKY; and for the > 52 wk group: SHR > BC1(S) = F1 > BC1(W) > WKY [F1 obtained from SHR .times. WKY: BC1(S) = SHR .times. F1; BC1(W) = WKY .times. 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 12-16 wk rats (but not from 6-8 wk rats) with 4 .times. 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. In addition, there was a good correlation, r = 0.59, between the mean arterial blood pressure of the SHR and related rats, and the ED50 ratio in the tail artery preparation but less so in other tissues: portal vein, 0.09; anococcygeus, 0.33. The results from the older > 52 wk group of rats again revealed similar noradrenaline ED50 values for the thoracic aorta, tail artery, portal vein and anococcygeus tissues prior to cocaine treatment, and after cocaine treatment there was, with the exception of aortic tissues, a good correlation between the mean arterial blood pressure of the rat and the noradrenaline ED50 ratio in the tail artery, r = 0.60; with lower r values for portal vein (0.47) and anococcygeus (0.33). Innervated arterial smooth muscle, as represented by the tail artery from > 52 wk SHR, apparently has an elevated postjunctional sensitivity to noradrenaline which is masked by an elevated uptake activity; the ED50 ratio for the tail artery preparation from the 12-16 wk animals is also higher in the SHR than WKY, suggesting elevated uptake activity; but the postjunctional sensitivity, after cocaine, is similar for SHR, F1 and WKY. No such differences, in either age group, are noted in the noninnervated thoracic aorta preparation. A comparison of the results from portal vein and anococcygeus indicates no significant differences in tissue sensitivity prior to cocaine treatment, but an elevated uptake activity in both portal vein and anococcygeus and elevated postjunctional sensitivity in the anococcygeus from SHR of the > 52 wk, but not the 12-16 wk group. Thus, elevated uptake activity is present at an earlier age in arterial smooth muscle from SHR than in venous or nonvascular smooth muscle, indicating selective changes occur in uptake in the arterial smooth muscle of the SHR prior to changes in nonarterial smooth muscle.