Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

Abstract

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.

The natriuretic and diuretic response to dopamine is maintained during rat pregnancy

“…This plasma volume expansion of pregnancy also occurs in animal models and is the result of net, continual renal sodium and fluid retention (1). Previous findings in our laboratory and others have indicated that in normal pregnancy the natriuretic response to atrial natriuretic peptide (ANP) is blunted, therefore promoting sodium retention and plasma volume expansion (7,12,15,16).ANP signals through the second messenger cGMP, and we have reported that PDE-5 activity and protein abundance in the inner medullary collecting duct are selectively increased in normal pregnancy (14). In addition, selective, intrarenal PDE-5 inhibition with sildenafil reverses the blunted response to infused ANP seen in normal pregnancy (10).…”

“…These data suggest that the renal response to natriuretic stimuli that act via the adenylyl cyclase-cAMP pathway is preserved during pregnancy. This is in contrast to the guanylyl cyclasecGMP pathway as the natriuretic response to ANP is blunted during pregnancy (7,12,15,16).…”

“…This plasma volume expansion of pregnancy also occurs in animal models and is the result of net, continual renal sodium and fluid retention (1). Previous findings in our laboratory and others have indicated that in normal pregnancy the natriuretic response to atrial natriuretic peptide (ANP) is blunted, therefore promoting sodium retention and plasma volume expansion (7,12,15,16).…”

Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat

“…Previous findings in our laboratory and from others have indicated that in normal pregnancy the natriuretic response to atrial natriuretic peptide (ANP) and the pressure-natriuresis response are blunted, therefore promoting sodium retention and plasma volume expansion (6,17,18,22,23). Pressureinduced natriuresis is dependent on the renal tubular actions of nitric oxide (NO, 16).…”

The Ouabain-Binding Site of the 2 Isoform of Na,K-ATPase Plays a Role in Blood Pressure Regulation During Pregnancy

“…The gestational plasma volume expansion is characterized by renal Na + and fluid retention. During normal pregnancy, natriuresis in response to atrial natriuretic peptide is remarkably reduced in rats16 and goats 17,18. The upregulation of aquaporin 2, a water channel expressed in the renal collecting duct, and a reduction of the osmotic thresholds for the vasopressin secretion and the perception of thirst during gestation also result in increased water intake and retention 14,19,20.…”