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 blood pressure and contractile force generation by subsequently isolated mesenteric resistance arteries was examined using the spontaneously hypertensive rat (SHR) model of genetic hypertension. Beginning at 6 weeks of age, male SHR were given daily intraperitoneal injections of vehicle, 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 resistance arteries were isolated for assessment of contractile function using a wire myograph. Blood pressure became elevated in the rats receiving 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 to nine, blood pressure continued to rise but was not different among the 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 elevated in the three groups treated with 1,25 (OH)2 vitamin D3 compared with control. The active stress response of resistance arteries to norepinephrine and arginine vasopressin was significantly elevated in rats that received 30 and 40 ng 1,25 (OH)2 vitamin D3, but no differences in apparent sensitivity to these agonists were detected. Acetylcholine-induced relaxation was unaltered in vessels pre-contracted with norepinephrine, but was enhanced in the group receiving 40 ng 1,25 (OH)2 vitamin 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.