The effects of anti-hypertensive therapy on the structural, mechanical andmetabolic properties of the rat aorta

The vascular system exhibits altered growth, calcium responses and metaboli sm during hypertension. To relate such changes, we compared histological, t ension and metabolic responses in the aorta from 32-week-old spontaneously hypertensive rats (SHRs), normotensive Wistar-Kyoto (WKY) rats, and SHRs tr eated with Verapamil (V) and ACE-inhibitor, Trandolapril (T) as well as a c ombination of the two treatments (C). Vascular hypertrophy was apparent in the SHRs. Contractile responses induced by 50 mmol/l KCl and 2.5 mmol/l Ca2 + were significantly lower in the SHR (64.4 mN/mm(2) vs. 49.2 mN/mm(2)), bu t an associated increase in Ca2+-sensitivity (EC50 of extracellular Ca2+ (m u mol/l): SHR, 456 vs. WKY, 616) normalised tension generating ability. All treatments led to significant decreases in blood pressure, although only T and C treated animals became normotensive with concomitant normalisation o f vascular hypertrophy. An increase in oxygen consumption was apparent in t he SHR aorta, which was associated with significant differences in the acti vities of key metabolic enzymes. Anti-hypertensive treatment normalised man y of the metabolic parameters, with the C therapy being the most efficaciou s. We conclude that the treatment of hypertension by combined therapy leads to a better normalisation of structural, contractile, and metabolic parame ters in the SHR, than either treatment alone and that metabolic changes wit h the pathology are resolved with appropriate therapy.