Effects of phenoxybenzamine, metoprolol, captopril, and meclofenamate on cardiovascular function in deoxycorticosterone acetate hypertensive Yucatan miniature swine.

Eight adult Yucatan miniature swine were implanted with deoxycorticosterone acetate (DOCA) impregnated silicone strips (100 mg X kg-1). After 16 weeks of DOCA treatment mean arterial pressure (MAP) increased to 183 +/- 4 mmHg (1 mmHg = 133.322 Pa). In four normal animals arterial pressure was 126 +/- 8 mmHg. The increase in MAP in the DOCA animals was due to an elevated total peripheral resistance (TPR) with cardiac output remaining normal. In tests with conscious animals, phenoxybenzamine (1 mg X kg-1) significantly decreased arterial pressure via a selective decrease in TPR. Neither meclofenamate, metoprolol, nor captopril affected MAP in these DOCA hypertensive animals. Dose--response curves to exogenous norepinephrine and angiotensin II revealed that the DOCA animals had an increased pressor sensitivity to both of these agents. These data suggest that in the DOCA hypertensive Yucatan swine an increase in alpha adrenergic activity and (or) an increase in smooth muscle responsiveness to circulating catecholamines is responsible for the increase in blood pressure as a result of an increase in total peripheral resistance.