Our study was designed to determine whether the calcium channel antagonists verapamil, diltiazem, and nifedipine and the nitrate vasodilator sodium nitroprusside modulate carotid sinus (CS) baroreflex control of mean arterial pressure (MAP) and heart rate (HR). Pentobarbital-anesthetized, vagotomized dogs were surgically prepared for reversible vascular isolation of the CS regions. Open-loop performance of the CS baroreflex was determined under control conditions and after intravenous infusion of each agent for 20 minutes at four rates (nitroprusside: 0.3-10 μg/kg/min; verapamil and diltiazem: 1-30 μg/kg/min; nifedipine: 0.1-3 μg/kg/min). With the CS baroreflex loop dosed, each vasodilator decreased MAP from control (nitroprusside: 127±3 to 69±5 mm Hg; verapamil: 137±7 to 86±5 mm Hg; diltiazem: 137±9 to 100±5 mm Hg; nifedipine: 140±6 to 109±7 mm Hg). Each compound also caused a dose-dependent downward shift in the open-loop CSP-MAP relations. The higher doses of each vasodilator also depressed the total range of control of MAP (i.e., maximum MAP minus minimum MAP) by the baroreflex and significantly attenuated the peak open-loop MAP/CSP gains (nitroprusside: 1.21±0.19 to 0.56±0.12; verapamil: 1.36±0.16 to 0.64±0.10; diltiazem: 1.52±0.34 to 0.89±0.11; nifedipine: 1.35±0.20 to 0.83±0.14) but did not alter the CSP at which the peak gain was manifest. Only verapamil and diltiazem significantly shifted downward the CSP-HR relations, whereas none of the drugs affected the total range of baroreflex control of HR (i.e., maximum HR minus minimum HR) or the peak open-loop HR/CSP gains. Our results suggest that 1) it is unlikely that calcium channel antagonists act directly on the baroreceptors or the neural components of the baroreflex loop (i.e., afferent, central and efferent nerves) because they impair CS baroreflex control of MAP but not HR and 2) the impairment of MAP control is predominantly due to a nonspecific blunting of adrenergic vasoconstriction.