| Summary |
Cardiac membrane preparations from developing euthyroid and hypothyroid spontaneously hypertensive rats (SHR) and Kyoto Wistar (WKY) rats (0 to 125 days of age) were analyzed in an attempt to correlate biochemical changes with the known functional changes occurring with the development of hypertension in the SHR. Several membrane constituents which have been shown to influence myocardial contractility and may reflect sympathetic nervous system alterations were measured in myocardial preparations from SHR and WKY rats at various ages. These constituents included the apparent numbers of alpha- and beta-adrenergic receptors, adenylate cyclase activities and Na''',K''^- and K^,Ca^'*^-ATPase activities. The apparent number of both alpha- and beta-adrenergic receptors decreased as the rats aged. Isoproterenol-stimulated adenylate cyclase activities were significantly higher (P [less-than] 0.05) in the prehypertensive SHR when compared to WKY rats but declined to similar values as hypertension appeared. Both Na⁺,K⁺- and K⁺,Ca⁺⁺-ATPase activities were higher in the SHR, when compared to WKY rats (P [less-than] 0.05) at both pre- and post-hypertensive stages. Although not significant, the apparent numbers of cardiac alpha-and beta-adrenergic receptors were slightly elevated in the SHR. This, as well as the increased adenylate cyclase activity stimulated by isoproterenol during the prehypertensive stage may contribute to the onset of hypertension in the SHR. The elevated ATPase activities measured in the SHR may also be partially responsible for the altered reactivity of the SHR myocardium, resulting in hypertension. Treatment of both strains with methimazole resulted in hypothyroidism, lowered blood pressure below control values, and completely prevented the development of hypertension in the SHRs up to 125 days. The apparent number of both alpha- and beta-adrenergic receptors were similar in euthyroid and hypothyroid WKYs and SHRs. Membrane preparations from hypothyroid animals showed a decrease in all adenylate cyclase and Na⁺,K⁺- and K⁺,Ca⁺⁺-ATPase activities when compared to euthyroid controls. Hypothyroidism effectively prevents the onset of hypertension, suggesting these enzymic parameters play an integral part in the genesis of hypertension in the SHR. |
