Central muscarinic modulation of fetal blood pressure and heart rate

It has previously been demonstrated that the fetal lamb cardiovascular system can respond to peripheral muscarinic stimulation. However the role of central muscarinic mechanisms in modulating fetal cardiovascular function has not been described. Pilocarpine is a muscarinic agonist that readily crosses the blood-brain barrier and was therefore employed to examine both central and peripheral muscarinic mechanisms in modulating fetal cardiovascular function. Fetal lambs were prepared for chronic intrauterine recording of fetal blood pressure (FBP) and heart rate (FHR). Direct administration of pilocarpine to the fetus resulted in an immediate dose-dependent decrease in both systolic and diastolic blood pressure and a rapid fall in FHR. The initial phase of hypotension was very short-lived (1-2 min) and was subsequently followed by a significant increase in systolic, diastolic and pulse pressures (30-60 min). Fetal heart rate gradually returned to control levels by 30 min after pilocarpine administration. Atropine pretreatment was effective in completely blocking the cardiovascular actions of pilocarpine, while methylatropine was only able to block the initial hypotensive and bradycardiac response. A prolonged tachycardia was also unmasked by methylatropine pretreatment. These data suggest that the initial hypotension and bradycardia in response to pilocarpine administration are mediated via peripheral muscarinic receptors, while stimulation of central muscarinic receptors result in hypertension and tachycardia. These data confirm that, as in the adult, central cholinergic mechanisms are involved in the modulation of cardiovascular function in the developing fetus.