Interaction between beta blockers and epinephrine on hemodynamics of spontaneously hypertensive rats

Hypertensive patients treated with nonselective beta adrenergic blocking agents may show remarkable hemodynamic changes with administration of epinephrine clinically. We have attempted to investigate the effects of the interaction between beta blockers (a nonselective beta blocker, pindolol, and a cardioselective beta blocker, acebutolol) and a solution of 2% lidocaine containing 1:80,000 epinephrine on the hemodynamics of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), as compared with the normotensive rats. The blood pressures (systolic and diastolic) and heart rate were measured indirectly by the photoplethysmographic tail cuff method. All drugs were administered intraperitoneally. We found that: (1) epinephrine with pindolol or acebutolol pretreatment did not cause significant hemodynamic changes in WKY; (2) in SHR, epinephrine in combination with pindolol induced remarkable hemodynamic changes (in particular, increase in diastolic blood pressure), which were prevented by phentolamine pretreatment, whereas epinephrine with acebutolol pretreatment induced no significant hemodynamic changes in these animals; (3) epinephrine in combination with pindolol caused pulmonary congestion or edema in SHR; this was confirmed by both quantitative analysis and histological investigations. These results suggest that pindolol blocked both beta 1 and beta 2 receptors, and therefore, this resulted in exaggerated alpha effects of epinephrine, a remarkable systemic vasoconstriction, and pulmonary congestion. In a clinical setting, great caution should be paid to the hypertensive patients, who are being treated with nonselective beta blockers, if epinephrine-containing local anesthetics are administered.