Central C-type natriuretic peptide but not atrial natriuretic factor lowers blood pressure and adrenocortical secretion in normal conscious sheep.

C-type natriuretic peptide (CNP) and its specific receptor (ANPRB) are richly distributed throughout the brain, especially the anterior pituitary and hypothalamus but not in tissue of nonneural origin. These findings suggest that the actions of CNP, unlike atrial natriuretic factor (ANF), are largely confined to the brain where CNP may participate in the central regulation of hemodynamics and salt and water balance. Therefore, we have studied the hemodynamic, renal, and hormonal effects of continuous intracerebroventricular infusions of CNP (5 micrograms/h for 4 h) in a vehicle-controlled study and compared the responses to those of ANF in normal conscious sheep. Hemodynamic and hormonal responses to ANF were not different from control infusions. There was a trend for urinary sodium and potassium excretion to increase throughout the control infusion but not on the ANF day. Water intake during control infusion (358 +/- 160 ml/4 h) was almost 3-fold that ingested during ANF (127 +/- 89 ml/4 h, NS). In contrast, CNP induced a prompt fall in mean arterial pressure (mean decrement 5 mm Hg), arterial pressure remaining below time control values for the remainder of the infusion (P = 0.006). Rises in both heart rate and PRA observed on the control day tended to be attenuated by CNP. Urine electrolyte response to CNP was similar to that observed with ANF. Compared with control infusions, the responses of both plasma aldosterone (P = 0.006) and cortisol (P = 0.043) were significantly different. Following CNP-induced hypotension, plasma cortisol and aldosterone increased abruptly at 30 min after which values fell to control or lower levels until the infusion was terminated. These studies show that intracerebroventricular CNP lowers arterial pressure without increasing heart rate and also suppresses the adrenocortical response, whereas ANF given under the same conditions has no significant effects. These data support the hypothesis that CNP plays an important role in the central regulation of blood pressure and hormones.