Cardiovascular and renal effects of calcitonin gene-related peptide in hypertensive dogs

The systemic cardiovascular and renal effects of synthetic β-human calcitonin gene-related peptide (β-hCGRP) were examined in conscious normotensive and one-kidney one-clip (1K-1C) hypertensive dogs. β-hCGRP was infused intravenously at 10 and 50 ng/kg/min for 75-min periods each. Mean arterial pressure did not change significantly (p>0.05) in either group during low dose infusion of β-hCGRP, but infusion of β-hCGRP at 50 ng/kg/min produced a fall in mean arterial pressure from 140±4 to 116±6 mmHg (p<0.05) in the hypertensive dogs (n=4) and from 100±4 to 78±3 mmHg (p<0.05) in the normotensive dogs (n=4). Heart rates increased significantly during infusion of β-hCGRP in both groups. Also, renal sodium and potassium excretion decreased (p<0.05) in the two groups at both the low and high doses of β-hCGRP. Creatinine clearance was unchanged in normal dogs and decreased (p<0.05) in 1K-1C hypertensive dogs at the high rate of β-hCGRP infusion. The clearance of p-aminohippurate increased approximately 20% (p<0.05) in both groups with the low dose infusion of β-hCGRP but further increases were elecited only in the normotensive dogs in response to the elevation in the β-hCGRP infusion rate. Plasma renin and aldosterone levels increased (p<0.05) above control levels during the maximum hypotensive response to β-hCGRP infusion in both groups. These data indicate that β-hCGRP is a potent blood pressure lowering agent with important effects on renal hemodynamics and excretory function in both normotensive and 1K-1C hypertensive dogs during sustained intravenous infusions.