ADRENERGIC DYSFUNCTION IN UREMIA

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The partially nephrectomized uremic rat provides an excellent model to examine the effect of uremia on the adrenergic nervous system. Employing the uremic rat mesenteric vascular preparation, and the Gamma 1, selective radioligand (125I) IBE2254, the effect of uremia on the adrenergic effector component of systemic vascular resistance; the Gamma 1, vascular receptor, will be assessed. The hypothesis to be tested is chronic uremia results in a neurogenic form of hypertension, similar to that observed in experimental models with baroreceptor differentation. In such models, loss of tonic inhibition of sympathetic vasomotor outflow, results in sympathetically mediated vasoconstriction, increased catecholamine synthesis and hypertension. Specific objectives include: 1) To determine if the number of Gamma 1 vascular receptors is decreased in uremic rats. Physiologic states characterized by increased endogenous levels of catecholamines have been associated with down regulation of Gamma 1 vascular receptors. By determining plasma catecholamine levels, we will be able to correlate these with any changes in receptor number observed. 2) To determine if the affinity of the Gamma 1 vascular receptor is blunted or decreased by the uremic state. In a series of related investigations also performed in the uremic rat model, the effect of chronic uremia on density and affinity of myocardial B adrenergic receptors; and B receptor; adenyl cyclase coupling, will be examined.