MODULATION OF ENDOTHELIN EFFECTS ON BLOOD-PRESSURE AND HEMATOCRIT BY ATRIAL-NATRIURETIC-PEPTIDE

Infusion of endothelin has been observed to increase hematocrit, and the peptide also stimulates release of atrial natriuretic peptide (ANP) both in vitro and in vivo. We studied the relation of these two actions of endothelin in anesthetized, bilaterally nephrectomized Sprague-Dawley rats. Infusion of endothelin (25 ng/kg/min) for 45 minutes produced a modest increase in blood pressure of 12% from a baseline of 99 +/- 5 mm Hg and an increase in hematocrit of 8.0 +/- 0.6%, reflecting a reduction in plasma volume of 13.1 +/- 0.9%. These changes each exceeded greatly those observed after 45 minutes of vehicle infusion. Plasma protein concentration, however, increased only by 4.2 +/- 0.6%, suggesting protein extravasation, which was confirmed by finding an endothelin-dependent increase in the accumulation of Evans blue dye in heart, skeletal muscle, and intestine, but not liver, lung, brain, or testis. Endothelin infusion increased plasma immunoreactive ANP concentration from 196 +/- 50 to 722 +/- 203 pg/ml (p < 0.02), and a close correlation existed between the increase in plasma immunoreactive ANP and immunoreactive endothelin concentrations as a result of the infusion (r = 0.84, p < 0.01). Pretreatment of rats with rabbit anti-rat ANP antiserum did not affect baseline variables but led to an exaggerated increase in blood pressure (25.3 +/- 2.9%, p < 0.002 versus endothelin alone). No change in hematocrit occurred. Thus, the increase in plasma immunoreactive ANP concentration resulting from endothelin infusion mediates the increase in hematocrit through an increase in vascular permeability to whole plasma. The exaggerated pressor effect of the infused endothelin in the presence of ANP antiserum suggests that ANP may modulate the vasoconstrictor actions of endothelin in vivo.