EFFECT OF LONG-TERM ADMINISTRATION OF 125 (OH)2 VITAMIN-D(3) ON BLOOD-PRESSURE AND RESISTANCE ARTERY CONTRACTILITY IN THE SPONTANEOUSLY HYPERTENSIVE RAT

The effect of long-term daily injection of 1,25 (OH)2 vitamin D3 on bl ood pressure and contractile force generation by subsequently isolated mesenteric resistance arteries was examined using the spontaneously h ypertensive rat (SHR) model of genetic hypertension. Beginning at 6 we eks of age, male SHR were given daily intraperitoneal injections of ve hicle, or 1,25 (OH)2 vitamin D3 at 20, 30, or 40 ng/100 g body weight. Body weight and systolic blood pressure were determined weekly. After 9 weeks, serum was prepared for electrolyte analysis and mesenteric r esistance arteries were isolated for assessment of contractile functio n using a wire myograph. Blood pressure became elevated in the rats re ceiving 20 and 40 ng 1,25 (OH)2 vitamin D3 after 5 weeks and remained elevated in the 40 ng group during the sixth week. Between weeks six t o nine, blood pressure continued to rise but was not different among t he groups. In addition, during the period between 6 and 9 weeks, there was a decline in the rate of weight gain in rats receiving 30 and 40 ng 1,25 (OH)2 vitamin D3. Serum ionized Ca2+ was significantly elevate d in the three groups treated with 1,25 (OH)2 vitamin D3 compared with control. The active stress response of resistance arteries to norepin ephrine and arginine vasopressin was significantly elevated in rats th at received 30 and 40 ng 1,25 (OH)2 vitamin D3, but no differences in apparent sensitivity to these agonists were detected. Acetylcholine-in duced relaxation was unaltered in vessels pre-contracted with norepine phrine, but was enhanced in the group receiving 40 ng 1,25 (OH)2 vitam in D3 when pre-relaxation tone was induced with arginine vasopressin. We conclude that chronic injection of 1,25 (OH)2 vitamin D3 increases active stress generation by resistance arteries but has only a slight increase in the normal rise in blood pressure in the growing SHR.