ANP, BNP, and CNP enhance bradycardic responses to cardiopulmonary chemoreceptor activation in conscious sheep

We demonstrated previously that atrial natriuretic peptide (ANP) enhances r eflex bradycardia to intravenous serotonin [5-hydroxytryptamine (5-HT)] (vo n Bezold-Jarisch reflex) in rats. To determine whether 1) ANP affects this cardiopulmonary vagal reflex in another species and 2) B-type (BNP) and C-t ype (CNP) natriuretic peptides share with ANP the ability to modulate this reflex, we used intravenous phenylbiguanide (PBG), a 5-HT3 agonist, as the stimulus to evoke a von Bezold-Jarisch reflex (dose-related, reproducible b radycardia) in conscious adult sheep (n = 5). Three doses of PBG (13 +/- 3, 20 +/- 3, and 31 +/- 4 mug/kg) injected into the jugular vein caused refle x cardiac slowing of -7 +/- 1, -15 +/- 2, and -36 +/- 3 beats/min, respecti vely, under control conditions. These doses of PBG were repeated during inf usions of ANP, BNP, or CNP (10 pmol.kg(-1).min(-1) iv), or vehicle (normal saline). Each of the natriuretic peptides significantly (P < 0.05) enhanced the sensitivity of bradycardic responses to PBG by 94 +/- 8% (ANP), 142 +/ - 55% (BNP), and 61 +/- 16% (CNP). Thus not only did ANP sensitize cardiopu lmonary chemoreceptor activation in a species with resting heart rate close to that in humans, but BNP and CNP also enhanced von Bezold-Jarisch reflex activity in conscious sheep.