Inadequate blockade by hexamethonium of the baroreceptor heart rate response in anesthetized and conscious rats

The ability of hexamethonium (HEX) alone or in combination with atropine methylbromide (AMB) to block the heart rate (HR) response to baroreceptor activation by phenylephrine (PE) or angiotensin II (AII)-evoked increments in blood pressure was evaluated in rats. A highly significant negative correlation existed under control conditions between the changes in MAP and HR. HEX (10-20 mg/kg) did not influence the baroreceptor HR response of anesthetized and conscious rats, suggesting anesthesia was not involved in the failure of HEX to abolish the baroreceptor HR response. A combination of HEX and AMB (full ganglionic blockade) substantially attenuated but did not abolish the HR response to baroreceptor activation, but this effect was not significantly different from that produced by AMB alone. In a marked contrast to HEX, chlorisondamine (CHL) abolished the baroreceptor HR response both in anesthetized and in conscious rats. Efficacy of ganglionic blockade was tested by examining the effects of HEX or CHL on the frequency-bradycardic response relationship evoked by electrical stimulation of the peripheral end of the right vagus; HEX only attenuated the response whereas CHL abolished it. It is concluded that, even in doses which lower blood pressure, HEX: 1) does not adequately block the baroreceptor HR response; 2) when combined with a muscarinic blocker to induce full ganglionic blockade, the decrease in baroreceptor HR response is largely, if not totally, attributable to muscarinic blockade; 3) is much weaker than CHL in blocking ganglionic transmission and, even when combined with a muscarinic blocker, it does not abolish the baroreceptor HR response whereas CHL does, and 4) CHL represents a better choice for studies that require complete ganglionic blockade in anesthetized or conscious rats.