Background Sympathetic and parasympathetic influences on heart rate (HR),
which are governed by baroreflex mechanisms, are integrated at the cardiac
sinus node through hyperpolarization‐activated cyclic nucleotide–gated
channels (HCN4). We hypothesized that HCN4 blockade with ivabradine
selectively attenuates HR and baroreflex HR regulation, leaving baroreflex
control of muscle sympathetic nerve activity intact. Methods and Results We
treated 21 healthy men with 2×7.5 mg ivabradine or placebo in a randomized
crossover fashion. We recorded electrocardiogram, blood pressure, and muscle
sympathetic nerve activity at rest and during pharmacological baroreflex
testing. Ivabradine reduced normalized HR from 65.9±8.1 to 58.4±6.2 beats per
minute (P<0.001) with unaffected blood pressure and muscle sympathetic nerve
activity. On ivabradine, cardiac and sympathetic baroreflex gains and blood
pressure responses to vasoactive drugs were unchanged. Ivabradine aggravated
bradycardia during baroreflex loading. Conclusions HCN4 blockade with
ivabradine reduced HR, leaving physiological regulation of HR and muscle
sympathetic nerve activity as well as baroreflex blood pressure buffering
intact. Ivabradine could aggravate bradycardia during parasympathetic
activation
