Does atrial natriuretic factor protect against right ventricular overload? I. Hemodynamic study

Abstract

We studied the effects of synthetic atrial natriuretic factor (ANF, 28-amino acid peptide) on base-line perfusion pressures and pressor responses to hypoxia and angiotensin II (ANG II) in isolated rat lungs and on the following hemodynamic and renal parameters in awake, chronically instrumented rats: cardiac output (CO), systemic (Rsa) and pulmonary (Rpa) vascular resistances, ANG II- and hypoxia (10.5% O2)-induced changes in Rsa and Rpa, and urine output. Intra-arterial ANF injections lowered base-line perfusion pressures and blunted hypoxia- and ANG II-induced pressor responses in the isolated lungs. Bolus intravenous injection of ANF (10 micrograms/kg) into intact rats decreased CO and arterial blood pressures of both systemic and pulmonary circulations and increased Rsa. ANG II (0.4 micrograms/kg) increased both Rsa and Rpa, and hypoxia increased Rpa alone in the intact rats. ANF (10 micrograms/kg) inhibited both ANG II- and hypoxia-induced increases in Rpa but did not significantly affect the ANG II-induced increase in Rsa. The antagonistic effect of ANF on pulmonary vasoconstriction was reversible and dose-dependent. The threshold doses of ANF required to inhibit pulmonary vasoconstriction were in the same range as those required to elicit diuresis and natriuresis. The data demonstrate that ANF has a preferential relaxant effect on pulmonary vessels constricted by hypoxia or ANG II. Both the renal and the pulmonary vascular effects of ANF may represent fundamental physiological actions of ANF. These actions may serve as a negative feedback control system that protects the right ventricle from excessive mechanical loads.

Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide

“…ANP and BNP are cardiac hormones with natriuretic, diuretic and vasodilator actions [21, 22, 23, 24]. Previous studies in animal models have shown that ANP and BNP attenuate hypoxic pulmonary vasoconstriction [25, 26, 27]and inhibit ET-1 production or secretion via stimulation of cyclic GMP in cultured endothelial cells [14, 15]. Our findings suggest that in patients with COPD, plasma ANP and BNP levels increase in proportion to the increase in plasma ET-1 levels, and they act as functional antagonists of the vasoconstrictive effect of ET-1 in the pulmonary circulation.…”

The role of the renin‐angiotensin and natriuretic peptide systems in the pulmonary vasculature.

“…In this respect, the interaction of vasoactive agents with the hypoxic pulmonary vasoconstrictor response has generated much interest particularly where the observed increase in plasma ANP levels during hypoxia [45] suggests a possible counter-regulatory role. In the rat isolated, blood-perfused lung, ANP and BNP can attenuate the increase in PAP induced by hypoxia [58,59]. In vivo, ANP attenuates the acute vasoconstrictor response to hypoxia in pigs [53].…”

“…In vitro studies have demonstrated the vasorelaxant properties of ANP in pulmonary vessels preconstricted by ANG II [58,68]. There appears to be no equivalent in vivo evidence from animal studies although recent work in normal humans has examined this interaction and the intact pulmonary vasculature.…”

Role of atrial natriuretic factor in lung physiology and pathology.

“…The reason for this increased responsiveness during hypoxia remains unclear. Finally, ANF is capable of blocking the pulmonary pressor response to acute hypox ia in rats (86,102,103), cats, and pigs (104) but not in dogs (105).…”