Blood pressure, lanthanum-, and norepinephrine-induced mechanical response in thoracic aortic tissue

The responses of isolated thoracic aortic rings to 10(-5) M norepinephrine (NE) and 5 mM lanthanum chloride (La3+) were compared in tissues from 6- to 8-week-old and 12- to 16-week-old rats. Twelve strains of rats were selected: spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), genetically related outcross F1 and F2, backcross BC1(S) and BC1(W), and Wistar, SHR/Wistar, and Wistar/WKY crosses, Sprague-Dawley (SD), and also Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The La3+ response, expressed as the percentage of the maximal response to NE, demonstrated both age and blood pressure (BP) components in the SHR, WKY, F1, F2, and BC rats; however, when the La3+ response was expressed as mg force/mg tissue, no significant differences within these same groups were noted. The magnitude of the NE response in the same group of rats was inversely related to the BP of the 12- to 16-week-old animals (r = -0.45), and was not affected by treatment of the animal from conception with alpha-methyldopa. Aortic tissues from DS, but not DR or SD rats, demonstrated a response to La3+ which increased with the BP of the rat. This was not observed in prehypertensive DS rats and was prevented by the control of hypertension with either hydrochlorothiazide or MK-421 (a converting-enzyme inhibitor). We conclude that the reduced NE response in aortic tissues from SHR and related hypertensive rats reflects an inherent defect in the vascular smooth cell of the rat and is unaffected by BP control with antihypertensive drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)