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Chemosensitive cardiopulmonary afferents and the haemodynamic response to simulated haemorrhage in conscious rabbits

1 We set out to test whether the signal from the heart that initiates the decompensatory phase of acute central hypovolaemia in conscious rabbits is conveyed by chemosensitive afferents. 2 Haemorrhage was simulated by inflating an inferior vena caval cuff so that cardiac output fell at a constant rate of 8% of its baseline level per min. After sham or vehicle treatments the haemodynamic response had two phases. In the first, sympathoexcitatory, phase systemic vascular conductance fell in proportion to cardiac output so that mean arterial pressure fell by only 13 mmHg. When cardiac output had fallen by ∼50% a second, sympathoinhibitory, phase supervened. There was an abrupt rise of systemic vascular conductance and an abrupt fall of mean arterial pressure, to ∼40 mmHg. 3 The sympathoinhibitory phase was prevented by injection of the δ‐opioid antagonist ICI 174864 (100–300 nmol) or the μ‐opioid agonist H‐Tyr‐d‐Ala‐Gly‐MePhe‐NH(CH2)2OH (DAMGO) (100–300 pmol) into the fourth cerebral ventricle. 4 5‐HT3 receptors on myocardial or pulmonary afferents were excited by injection of ascending doses of phenylbiguanide (6.25–400 μg) into the left or right atrium respectively. Neuronal‐type nicotinic cholinoceptors in the epicardium were excited by injecting ascending doses of nicotine bitartrate (6.25–400 μg) into the pericardial sac. Each of these treatment regimens caused a reproducible, dose‐dependent, fall in mean arterial pressure. Intravenous injection of the 5‐HT3 antagonist MDL 72222 (1.0 mg kg−1) markedly attenuated the responses to phenylbiguanide. Intrapericardial injection of the neuronal‐type nicotinic cholinoceptor antagonist mecamylamine HCl (0.1 mg kg−1) abolished the effects of intrapericardial nicotine. Neither of these treatments affected the haemodynamic response to simulated haemorrhage. 5 Injection into the fourth ventricle of ICI 174864 (100–300 nmol) or DAMGO (100–300 pmol) had no effects on the dose‐response relationships for phenylbiguanide or nicotine. 6 We conclude that the cardiac afferents responsible for initiating the sympathoinhibitory phase of simulated haemorrhage in conscious rabbits do not correspond to the populations of phenylbiguanide‐sensitive cardiopulmonary afferents, nor to the population of nicotine‐sensitive epicardial afferents. We also conclude that the reflex haemodynamic responses to atrial phenylbiguanide and intrapericardial nicotine do not depend on an endogenous δ‐opioid receptor mechanism in the brainstem, and are not affected by exposure of the brainstem to exogeneous DAMGO.