Baroreflex and vagal mechanisms modulating left ventricular contractile responses to sympathomimetic amines in conscious dogs.

The steady state effects of intravenous norepinephrine (NE), 0.2 fig/kg per min, isoproterenoL 0.02 pg/kg per min, and dopamine, 10 pg/kg per min, on measurements of arterial and left ventricular (LV) pressures, dP/dt, LV diameter, and velocity of shortening were compared before and after muscarinic blockade with atropine sulfate or methyl atropine bromide (0.1 mg/kg). In intact conscious dogs, NE increased mean arterial pressure by 24 ± 2 mm Hg and LV dP/dt by 1140 ± 90 mm Hg/sec, but did not change LV velocity significantly and decreased heart rate by 13 ± 3 beats/min. After muscarinic blockade, NE caused significantly greater (P < 0.01) increases in mean arterial pressure of 49 ± 6 mm Hg, LV dP/dt of 3290 ± 240 mm Hg/sec, LV velocity of 24 ± 6 mm/sec, and heart rate of 7 ± 3 beats/min. A similar augmentation of the contractile response to infusions of isoproterenol and dopamine was observed following muscarinic blockade. These responses were dependent neither on arterial baroreceptors nor on an intact sympathetic nervous system. After vagotomy and arterial baroreceptor denervation (ABD), NE increased LV dP/dt by 2970 ± 170 mm Hg/sec and LV velocity by 20 ± 4 mm/sec, i.e., by amounts similar to those found after muscarinic blockade for intact dogs and dogs with ABD. However, in dogs with ABD and vagotomy, the contractile responses to NE were not augmented further by muscarinic blockade. Thus, the parasympathetic nervous system can exert a powerful inhibitory influence on the inotropic responses to infused sympathomimetic amines since, after muscarinic blockade, the inotropic responses to NE, isoproterenol, and dopamine increase 2-fold. The mechanism is independent of the arterial baroreceptor reflex and the sympathetic nervous system and appears to involve an inhibitory action of vagally released acetylcholine on the /3-adrenergic inotropic response to sympathomimetic amines. Ore Res 44:195-207, 1979