We compared responses to
BAY y 5959, which increases inotropy and decreases chronotropy, with those to
norepinephrine (NE), which coincidentally exerts the same directional effects on inotropy and chronotropy, albeit through different mechanisms, in the presence and absence of ganglionic blockade both in control and in HF. Both
BAY y 5959 and NE elicit direct effects on the heart and indirect effects through activation of reflexes, primarily the sinoaortic baroreceptor reflex.
BAY y 5959 still reduced heart rate in dogs with arterial baroreceptor
denervation, but not after ganglionic blockade. HF induced classic
catecholamine desensitization to the inotropic effects of NE and blunted reflex
bradycardia. In contrast, inotropic responses to
BAY y 5959 were preserved in HF. Surprisingly, the autonomically mediated
bradycardia induced by
BAY y 5959 was also preserved in HF. Baroreflex sensitivity was assessed in control and in HF by pulse interval-systolic arterial blood pressure (PI/SAP) slopes constructed in response to pharmacological alterations in arterial pressure. HF depressed the PI/SAP slope from 11.5+/-1.3 to 4.8+/-0.9 ms/mm Hg, but during
BAY y 5959 infusion in HF, the PI/SAP slope was restored to 24.1+/-5.2 ms/mm Hg. To assess central versus peripheral actions of
BAY y 5959, the agent was infused with intra-carotid artery perfusion at a low dose, which acted centrally but did not have an effect peripherally. Under these conditions, it still decreased heart rate and restored baroreflex sensitivity (PI/SAP slope, 12.7+/-2.8 ms/mm Hg).
CONCLUSIONS: