Vagal mediation of the effects of atrial natriuretic factor on blood pressure and arterial baroreflexes in the rabbit.

Abstract

We investigated the hemodynamic effect of synthetic atrial natriuretic factor Auriculin A (ANF) and its influence on arterial baroreflex control of heart rate, systemic blood pressure, and perfuslon pressure in the hind limb (perfused at constant flow) in rabbits anesthetized with a-chloralose and urethane. The neural mechanisms underlying these effects were also studied. In the intact animal, a 45-minute constant infusion of ANF (2 /xg/kg prime, 0.2 /ig/kg/min) significantly reduced mean blood pressure and increased mean perfusion pressure, while heart rate did not change. Comparable data were obtained with lower (0.5 fj-gfkg + 0.05 /xg/kg/min; 1 /tg/kg + 0.1 /xg/kg/mln) or higher (4 Mg/fcg + 0.4 /xg/kg/min; 8 /xg/kg + 0.8 /ig/kg/min) doses of ANF. In addition, ANF enhanced bradycardic reflex responses to phenylephrine i.v. bolus administration, while it did not change baroreflexmediated responses to nitroglycerin i.v. bolus administration and to 30-second bilateral carotid occlusion. The specificity of the influence of ANF on arterial baroreflex responses was confirmed by the observation that no significant change in reflex responses to phenylephrine or carotid occlusion was detectable during a comparable decrease in blood pressure induced by a constant infusion of nitroglycerin. Bilateral vagotomy prevented both the fall in blood pressure and the increase in perfusion pressure induced by ANF, while cholinergic blockade (atropine, 0.5 mg/kg i.v.) or adrenergic blockade (propranolol, 0.3 mg/kg i.v. + phentolamine, 0.3 mg/kg i.v.) did not modify the hemodynamic response to ANF observed in the intact animal. The ANF-induced enhancement of the reflex bradycardie response to phenylephrine-induced rise in blood pressure was prevented by both vagotomy and atropine. In conclusion, our data suggest that in this experimental model an increase in parasympathetic tone is involved in the blood pressure lowering effect of synthetic ANF as well as in the potentiation of the reflex brady cardie response to phenylephrine-induced arterial baroreceptor loading caused by the peptide. (Circulation Research 1987;60:747-755) I n their initial studies on atrial natriuretic factor (ANF), de Bold and coworkers 1 observed that, in addition to the characteristic natriuretic effect, the injection of atrial extracts in rats induced a slight but consistent reduction in blood pressure. This effect was later confirmed with synthetic ANF peptides in both conscious and anesthetized normotensive and hypertensive animals 2 " 9 and in man. 10 " 13The blood pressure lowering effect of ANF was originally attributed to its vasodilator properties, but recent studies seem to indicate that more complex hemodynamic mechanisms are involved in the response to ANF administration. In particular, it has been reported that bolus or sustained infusion of ANF can lower cardiac output.914 " 16 The intrinsic mechanisms that lead to a reduction in cardiac output in response to ANF have not yet been defined. In this regard, Ackermann et al 17 showed that the hypo...

Correlation Between Atrial Natriuretic Peptide and Baroreflex Sensitivity in Patients With Congestive Heart Failure

“…In the present study, we found no significant correlation between a decrease of BRS and overactivation of sympathetic nervous system, but a direct relationship was observed between a low BRS and an increased ANP level. Our observational relationship between BRS and ANP was consistent with the recent observation of Volpe 25 and the study of Ebert 27 with exogenous administration of ANP, suggesting a restoration of the impairment BRS with ANP. We could not find any significant relationship between BRS and catecholamines, which might be explained by the fact that our heart failure patients were relatively mild and stable, and that ANP is the most sensitive neurohumoral factor indicating the severity of heart failure.…”

“…Volpe et al reported that ANP sensitized vagal afferents and that it exerted a selective influence on baroreflex responses to hypertensive stimuli. 25 In the rat, it has also been reported that reflex tachycardia and sympathoexcitation did not occur during hypotension caused by ANP, whereas similar levels of hypotension produced with nitroglycerin provoked an appropriate reflex tachycardic response. 23,24 Vagotomy did reverse these inhibitory effects of ANP, but atropine did not.…”

“…[13][14][15][16][17][18]21 The principal action of ANP is diuresis and vasodilation, but it influences autonomic activity as well and ANP administration has been shown to alter BRS. [22][23][24][25][26][27] Thus, it appears that heart failure may involve interactions between the baroreflex, as neural circulatory regulation, and humoral factors acting as compensatory mechanisms. In the present study, we investigated the relationship between BRS and humoral factors in patients with chronic heart failure.…”

Effects of atrial natriuretic factor on baroreceptor reflexes.

“…Ferrari et al 1 considered the possibility that ANF increased vagal influences on the heart. Volpe et al 7 came to the same conclusion with the findings that ANF potentiated reflex bradycardia, and this effect of ANF was prevented by vagotomy and atropine. However, there are questions to be answered in this regard.…”

“…However, there are questions to be answered in this regard. First, Volpe et al 7 noted that increases in resting heart rate caused by vagotomy and atropine were small and comparable before and after intravenous ANF. The latter results appear to contradict the suggestion of increased resting vagal activity induced by ANF.…”