Arterial reactivity, blood pressure, and plasma levels of atrial natriuretic peptides in normotensive and hypertensive rats: effects of acute and chronic administration of atriopeptin III.

We compared acute and chronic effects of atriopeptin III in normotensive and spontaneously hypertensive rats. Atriopeptin III relaxed isolated aortae and intrarenal microarteries but not coronary and mesenteric microarteries of normotensive rats. Effects on arterial smooth muscle were comparable in hypertensive and normotensive rats and were not affected by long-term treatment of the animals with the peptide. Acute administration of atriopeptin III (4-400 nmol/kg, intravenously) reduced systolic blood pressure in conscious spontaneously hypertensive and renal hypertensive rats but not in normotensive rats. In spontaneously hypertensive rats, nephrectomy increased the sensitivity to and the duration of the acute antihypertensive effect. Renal subcellular fractions rapidly inactivated atriopeptin III in vitro. This atriopeptinase activity was comparable for normotensive and spontaneously hypertensive rats and was not affected by long-term treatment of the rats with the peptide. Continuous administration of low doses of atriopeptin III (0.4 and 4.0 nmol/kg/h, intravenously (i.v.) during 7 days) caused a progressive reduction in systolic blood pressure in spontaneously hypertensive but not in normotensive rats. It did not affect plasma levels of aldosterone or renin and resulted in less than a doubling of the plasma levels of atrial natriuretic peptides. These findings confirm that atrial natriuretic peptides preferentially relax the renal microvasculature. They demonstrate that although atriopeptin III comparably relaxes arterial smooth muscle of normotensive and spontaneously hypertensive rats, both acute and chronic administration of the peptide preferentially lower blood pressure in hypertensive rats. Rather than contributing to the effects on blood pressure, the kidneys modulate the duration of action of atrial natriuretic peptides.