Prostacyclin (PGI2) lowers heart rate in the conscious dog

Prostacyclin (PGI2) and arachidonic acid (AA), the fatty acid precursor of the bisenoic prostaglandings (PG), are potent vasodepressor agents, similar in their action to PGE1 and PGE2; however, unlike these prostaglandings which increase heart rate, the administration of PGI2 or AA causes heart rate to fall. Injection of AA (20 mg) and PGI2 (20 μg), into conscious, trained dogs fitted with exteriorised carotid loops, resulted in a fall in mean arterial blood pressure (5.39 ± 0.49 and 5.57 ± 0.44 kPa) together with a reduction in heart rate (–5.7 ± 2.9 and –15.0 ± 3.9 beats·min−1, respectively). On the other hand, PGE2 (50 μg), PGE1 (50 μg) and sodium nitroprusside (500 μg), while causing similar or smaller decreases in blood pressure (2.45 ± 0.27, 3.68 ± 0.63 and 4.15 ± 0.35 kPa) induced the expected baroreflex-mediated increases in heart rate (50.1 ± 6.0, 63.1 ± 5.1 and 61.3 ± 1.8 beats·min−1, respectively). In contrast to these vasodepressor agents, PGI2 and AA also caused significant reductions in dP/dtmax. The bradycardia following PGI2 and AA was prevented by atropine and hexamethonium, signifying the participation of vagal efferent fibres in and the reflex nature of the response. The bradycardia, the hypotension and the changes in cardiac function caused by AA were blocked by indomethacin. Moreover, induction of anaesthesia with sodium pentobarbital inhibited the reflex bradycardia following PGI2 and AA. These experiments show that in the conscious dog, probably the best model for the study of reflex cardiovascular regulation, injection of PGI2 or stimulation of prostaglandin synthesis in situ by AA, results in a distinct, Bezold-Jarisch-like response. This cardiovascular response, unlike those that follow the administration of other vasodilator prostaglandins or nitroprusside, is characterised by decreases in heart rate, arterial blood pressure and dP/dtmax, a set of responses most likely mediated by the activation of cardiopulmonary receptors and vagal afferent and efferent fibres.