Hypertension is a sign that accompanies a number of different diseases of the central nervous system, the adrenal cortex, the adrenal medulla, the kidney, etc., or is of unknown etiology (essential hypertension). There is no certainty that the acute hypertension which immediately follows the IV or IP injection of Cd, and the chronic hypertension that follows its prolonged low-dosage ingestion, have the same mechanism. We propose to study the effect of pretreatment with vasodilators such as minoxidil, hydralazine and the thiazides, adrenergic blockers such as propanolon, practolol, etc., ganglionic blockers such as pentolinium, and inhibitors or angiotensin II or the converting enzyme on the acute response to IP cadmium. We will then use these same pretreatments on the arteries of rats that are in the subacute phase (i.e., when resting pressures are normal, but arterial responsiveness to vasoconstrictors in increased), and on the chronic hypertensive phase that follows prolonged treatment. We will also examine various dosage regimens and sensitizing procedures to determine the most reliable means of inducing cadmium hypertension, which is not known. Finally, we also intend to examine the pressor effects of other metallic ions such as Ni and Hg, and also retest the alleged inhibitory effect of some of them such as Se and Ca of Cd hypertension. They will be tested for their effects on the acute, sub-acute and chronic blood pressure responses to Cd. Histologic organ changes will be sought in many of these experiments.