Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

Effects of urodilatin (5, 10, 20, and 40 ng.kg(-1).min(-1)) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7-22% ) and urinary Na+ excretion (by 30, 76, 136, and 99% at 5, 10, 20, and 40 n g.kg(-1).min(-1), respectively). Glomerular filtration rate did not increas e significantly with any dose. The two lowest doses decreased cardiac outpu t (7 and 16%) and stroke volume (10 and 20%) without changing mean arterial blood pressure and heart rate. The two highest doses elicited larger decre ases in stroke volume (17 and 21%) but also decreased blood pressure (6 and 14%) and increased heart rate (15 and 38%), such that cardiac output remai ned unchanged. Hematocrit and plasma protein concentration increased with t he three highest doses. The renin-angiotensin-aldosterone system was inhibi ted by the three lowest doses but activated by the hypotensive dose of 40 n g.kg(-1).min(-1). Plasma vasopressin increased by factors of up to 5 during infusion of the three highest doses. Atrial natriuretic peptide immunoreac tivity (including urodilatin) and plasma cGMP increased dose dependently. T he urinary excretion rate of albumin was elevated up to 15-fold (37 +/- 17 mu g/min). Use of a newly developed assay revealed that baseline urinary ur odilatin excretion rate was low (<10 pg/min) and that fractional excretion of urodilatin remained below 0.1%. The results indicate that even moderatel y natriuretic doses of urodilatin exert protracted effects on systemic hemo dynamic, endocrine, and renal functions, including decreases in cardiac out put and renal blood flow without changes in arterial pressure or glomerular filtration rate, and that filtered urodilatin is almost completely removed by the renal tubules.