Mechanism of action of vasoconstrictor responses to atriopeptin II in conscious SHR

Abstract

Previous studies have demonstrated that infusion of synthetic atriopeptin II (AP II) lowered arterial pressure, reduced regional blood flow, and increased total peripheral and regional vascular resistances in conscious spontaneously hypertensive rats (SHR). This study was designed to examine the mechanism(s) involved in regional vasoconstrictor responses to AP II. In these experiments, hemodynamic actions of AP II were examined in control, 6-hydroxydopamine-treated (chemically sympathectomized), and renal-denervated groups of instrumented conscious SHR. Infusion of AP II (1 microgram X kg-1 X min-1) caused similar reductions in mean arterial pressure in control (-22 +/- 2 mmHg), chemically sympathectomized (-23 +/- 2 mmHg), and renal-denervated (-23 +/- 3 mmHg) SHR. In control SHR, AP II infusion reduced renal (-20 +/- 3%), mesenteric (-26 +/- 2%), and hindquarters (-18 +/- 10%) blood flow and increased regional vascular resistance in all three beds. Chemical sympathectomy prevented the fall in renal blood flow (RBF) and significantly abolished the regional vasoconstrictor responses to AP II infusion. In unilateral renal-denervated groups of SHR, AP II reduced renal vascular resistance (RVR) -11 +/- 3% but failed to alter RBF (-3 +/- 1%) in denervated kidneys. In contrast, RVR increased (20 +/- 7%) and RBF was significantly reduced (-29 +/- 3%) in contralateral-innervated kidneys. This study demonstrated that chemical or surgical destruction of renal sympathetic nerves abolished AP II-induced increases in RVR. These data further indicate that in conscious SHR the regional vasoconstrictor responses to AP II infusion appear to be mediated by increases in sympathetic tone rather than through direct vascular actions of AP II.

Hemodynamic effects of infusion versus bolus administration of atrial natriuretic factor.

“…Although infusion of the peptide at each dose for longer periods might have produced somewhat greater responses, infusion of the atrial peptides for 30 minutes 33 or longer (unpublished data) in conscious SHR caused quantitatively similar changes in the hemodynamic parameters as we observed during the 15-minute infusion period. Thus, even though the infusion periods for each dose of ANF were short (15 minutes), other studies from our laboratory indicate that the infusion periods are of ample duration to accurately illustrate the hemodynamic effects of ANF under steady state conditions.…”

“…15 The increase in regional vascular resistance appears to be mediated through increased sympathetic vasoconstrictor tone, rather than through direct vasoconstrictor actions of the peptide. 33 In these studies, surgical denervation or chemical sympathectomy abolished the regional vasoconstrictor responses to ANF infusion in conscious SHR. Even in sympathectomized rats, however, sustained renal vasodilator responses were not observed during the infusion of ANF.…”

“…After bolus administration, the sudden increase in circulating ANF may rapidly dilate renal resistance vessels, causing an increase in total renal blood flow before compensatory mechanisms can be activated. During an infusion, the slow but steady rise in plasma ANF may also relax renal vessels, but the dilation is negated and masked by increased sympathetic vasoconstrictor tone 33 or other vasoconstrictor mechanisms. However, even though total renal blood flow did not increase during infusion of ANF, one cannot rule out changes in the intrarenal distribution of blood flow by the atrial peptides.…”

Renal Hemodynamic Response to Atrial Natriuretic Factor in Fetal and Newborn Sheep

“…In summary, the present study demonstrates that ANF exerts direct vasodilator action on the fetal and neonatal renal vasculature and suggests that the decrease in renal blood flow previously observed during systemic infusion of ANF (3) was probably secondary to changes in systemic hemodynamics (22,25) and activation of compensatory mechanisms (18,19). Finally, it is shown that the renal vasodilatory response to intrarenal ANF infusion is similar in fetal and newborn sheep.…”

“…However, the present results suggest that ANF does not exert a direct vasoconstrictor action on the fetal and neonatal renal vasculature and that the site of administration of the peptide as well as the duration of the infusion play an important role in the renal hemodynamic response to ANF, as previously suggested in adults (17); systemic infusion of the peptide produces a renal vasoconstriction (3), whereas intrarenal bolus infusion produces renal vasodilation. One may speculate that systemic infusion of ANF increases sympathetic tone, which opposes the renal vasodilatory action of ANF (18,19), whereas ANF infused intrarenally is cleared rapidly by the kidney (20) and has little or no effect on sympathetic vasoconstrictor tone. In support of this hypothesis Lappe et al (1 8) have demonstrated that surgical denervation or chemical sympathectomy abolishes the renal vasoconstrictor response associated with systemic ANF infusion in spontaneously hypertensive rats.…”