Unexpected pressor responses to propranolol in essential hypertension. An interaction between renin, aldosterone and sympathetic activity.
The blood pressure response to propranolol treatment was analyzed retrospectively in 187 patients with benign essential hypertension. In most patients (102 patients, 54 per cent) systolic and/or diastolic blood pressure was decreased by more than 10 per cent (responders). No significant change in blood pressure occurred in 35 per cent (65 patients) of the patients (nonresponders). Surprisingly, in 20 patients (11 per cent) systolic (8 patients) and/or diastolic (14 patients) blood pressure was increased by more than 7 per cent (pressor-responders). All three subgroups received similar amounts of propranolol and irrespective of the effect on the blood pressure, propranolol produced a similar reduction in pulse rates, suggesting similar degree of beta blockade. The three subgroups did not differ in their clinical characteristics, except that the nonresponders were significantly older than the responders. Pretreatment renin values were highest in the responders, somewhat lower in the nonresponders and significantly lower in the pressor-responders. In a representative subset of 66 patients, control and treatment values for plasma renin activity and aldosterone excretion were compared. The responders had the most pronounced decreases in both renin and aldosterone. In striking contrast, no significant changes were observed in the two hormones in those patients whose blood pressure levels rose. Moreover, in the pressor-responders, the drug produced the greatest increases in body weight, reflecting sodium retention. The differences in blood pressure responses observed in different patients may be explained by various interplays between the drug-induced suppression of renin and aldosterone, and the operation of unapposed or reactive alpha sympathetic activity. The latter is presumably active in all patients tending to cause vasoconstriction and hence an increase in peripheral resistance. In the pressor-responders such unopposed alpha-tone combined with the demonstrated lack of renin and aldosterone suppression with attendant fluid retention could work to produce the paradoxical pressor responses. In contrast, in those whose blood pressure levels drop, the drug-induced suppression of renin leads to decreased peripheral resistance despite the unopposed alphatone. The accompanying decrease in aldosterone limits sodium retention and contributes to the fall in blood pressure levels.
D000328:Adult; D000367:Age Factors; D000450:Aldosterone / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003864:Depression, Chemical; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D000450:Aldosterone; D011433:Propranolol; D012083:Renin