Effects of Calcitonin Gene-Related Peptide on Renal Blood Flow in the Rat

Abstract

The effects of α-rat calcitonin gene-related peptide (α-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of α-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 ± 3 mm Hg to a maximal depressor response of 91 ± 2 mm Hg. During the first three doses of α-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 ± 0.3 ml/min to a peak level of 6.3 ± 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 ± 0.2 ml/min (P < 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of α-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of α-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 ± 0.06 to 0.14 ± 0.5 μEq/min (P < 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P > 0.05) from their respective baselines. These results demonstrate that α-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that α-rCGRP may have significant effects on the excretory function of the kidney.