EFFECTS OF ANGIOTENSIN-II AND PHENYLEPHRINE ON URINARY ENDOTHELIN IN NORMAL FEMALE VOLUNTEERS

Endothelin (ET) is a 21-amino acid peptide produced and secreted mainl y by endothelial cells. Small amounts of ET are found in plasma, where as large amounts are present in the urine. Despite the abundance of ET in the kidneys and urine, little is known about its regulation and cl inical significance. The present study was designed to examine the eff ects of angiotensin II (Ang II) and phenylephrine (Phe) on the excreti on of ET in normal female volunteers. Ang II and Phe were infused for 1 hour each and titrated to increase the mean arterial pressure by 20 mm Hg. There was a 60-minute recovery period before the second drug, a nd the order of the drugs was randomized. Infusion of Phe induced mild diuresis and natriuresis, which were associated with a significant in crease in the excretion of ET. In addition, Phe significantly increase d plasma atrial natriuretic factor (ANF). In contrast, infusion of equ ipressor doses of Ang II decreased urinary sodium excretion and did no t significantly alter the excretion of ET. Moreover, Ang II induced on ly a small and nonsignificant increase in plasma ANF. These results de monstrate that (1) physiological doses of Ang II do not affect excreti on of either ET or ANF; (2) Phe markedly increased the excretion of ET and ANF, independently of its effect on blood pressure; and (3) neith er agent changed plasma ET, but Phe increased plasma ANF. This is a US government work. There are no restrictions on its use.