DEVELOPMENT OF HYPERTENSION IN ANIMALS WITH REDUCED TOTAL PERIPHERAL RESISTANCE

The object of the present study was to determine whether deoxycorticosterone acetate (DOCA)-salt hypertension can be produced in rats in the presence of low total peripheral resistance (TPR) induced by long-term administration of minoxidil, a vasodilator. The rats were divided into four groups: sham-control, DOCA-salt, minoxidil, and DOCA-salt with minoxidil. The rats in both DOCA groups had DOCA pellets implanted subcutaneously and were given saline to drink. The rats in both minoxidil groups were given minoxidil (3 mg/day) in the drinking water throughout the experiment. Final measurements, including mean arterial blood pressure, cardiac index, and renal blood flow were made after 4-6 weeks. Flow measurements were made using radioactive microspheres. Cardiac index (ml . min-1 . 100 g-1) in sham-control rats averaged 18+/-2 and was higher in the other groups: 23+/-4 (DOCA-salt), 25+/-2 (minoxidil), and 30+/-2 (DOCA-salt plus minoxidil). Mean arterial pressure (mm Hg) was increased in both DOCA-salt rats (160+/-8) and DOCA-salt plus minoxidil rats (153+/-5) as compared with sham-control (116+/-2) and minoxidil (113+/-3) rats. There was no significant difference in TPR between the sham-control and DOCA-salt rats, but TPR in minoxidil and DOCA-salt plus minoxidil rats was 30% and 28% lower than that in untreated sham-control and DOCA-salt hypertensive rats, respectively. In contrast, renal vascular resistance was significantly increased in both DOCA-salt groups as compared with non-DOCA-salt groups. The results of this study show that long-term administration of minoxidil does not prevent the development of DOCA-salt hypertension, suggesting that an increase in TPR is not a necessary step in the development of DOCA-salt hypertension. Instead, increases in cardiac output were associated with the hypertension in all three experimental groups. These increases in cardiac output were more than sufficient to compensate for the decreases in TPR in the minoxidil and DOCA-salt plus minoxidil groups.