Effects of calcium channel blockers on isolated carotid baroreceptors and baroreflex

Abstract

Our study determined the effects of the calcium antagonists, nifedipine and verapamil, on the carotid sinus baroreceptors and baroreflex. The left carotid sinus region in dogs was vascularly isolated and filled with oxygenated physiological salt solution. Steady-state multiunit activity was recorded from the carotid sinus nerve for sinus pressures of 50-200 mmHg after bathing the carotid sinus region in a solution containing no drug, 10 micrograms/ml nifedipine (n = 6), or 5 micrograms/ml verapamil (n = 5). The slopes of the curves relating carotid sinus nerve activity (% of maximum control) to carotid sinus pressure were control, 0.81 +/- 0.06; nifedipine, 1.29 +/- 0.14; and verapamil, 0.48 +/- 0.06%/mmHg, indicating that nifedipine increased and verapamil decreased the sensitivity of the carotid sinus baroreceptors. Additional studies with bilateral carotid sinus isolation (carotid sinus nerves intact) indicated that nifedipine enhanced and verapamil attenuated carotid baroreflex control of renal sympathetic nerve activity. Pressure-volume curves generated in the isolated carotid sinus showed that effects on smooth muscle do not account for the opposing effects of the two Ca2+ antagonists. Omitting Ca2+ from the physiological solution resulted in increased carotid sinus nerve activity, an effect blocked by verapamil but not nifedipine. Verapamil, but not nifedipine, inhibited veratrine-induced (Na+-dependent) excitation of carotid baroreceptors. Thus the excitatory effects of nifedipine on the carotid sinus baroreceptors are dependent on Ca2+ mechanisms, whereas the inhibitory effects of verapamil may be due mainly to interference with the inward Na+ current.

Converting‐enzyme inhibition buffers the counter‐regulatory response to acute administration of nicardipine.

“…This is not in agreement with our findings with CGS 14 824 A. This discrepancy might be due to a specific effect of dihydropyridine on baroreflex function (Heesch et al, 1983) or to the higher reflex tachycardia ratio recorded in our work. It has been demonstrated that the speed of dihydropyridine intravenous administration greatly influences the degree of the tachycardia (Kleinbloesem et al, 1985).…”

Gadolinium inhibits mechanoelectrical transduction in rabbit carotid baroreceptors. Implication of stretch-activated channels.

“…Ca2+ channel antagonists of the dihydropyridine class either increased (32) or did not alter arterial baroreceptor discharge (29), and the dihydropyridine agonist Bay K8644 also did not affect baroreceptor discharge (30). The increased baroreceptor sensitivity seen with the L-type calcium channel blocker, nifedipine (32), is not consistent with a nonspecific block of Ca2+ channels by Gd3+ in our study, since Gd3+ inhibited rather than sensitized the mechano-responsiveness of the arterial baroreceptors. These observations and the recent report by Naruse and Sokabe (18) indicate that it is unlikely that inhibition of Ca2+ channels by Gd3+ can account for the blockade of the mechanoelectrical transduction mechanism.…”

The effects of acute and chronic dihydropyridine calcium antagonist therapy on baroreflex sensitivity: a re-analysis using the sequence method

“…Heesch and colleagues studied the effects of calcium antagonists on isolated carotid sinus baroreceptors and the baroreflex by applying the drugs locally to the carotid sinus region. 30 They demonstrated that verapamil and nifedipine had direct effects on the carotid sinus baroreceptors manifested in the reflex control of the efferent renal sympathetic nerve activity, whereas reflex control of blood pressure and heart rate was not affected. There was a difference between the two drugs; verapamil decreased and nifedipine increased the sensitivity of the carotid sinus baroreceptors and the baroreflex.…”