Urinary kallikrein activity, renal hemodynamics, and electrolyte handling during chronic beta blockade with propranolol in hypertension.

Propranolol has been reported to diminish renal perfusion and impair sodium excretion, but the relationship of these phenomena has not been well characterized during chronic propranolol administration in hypertensive man, nor has the potential involvement of the renal kallikreinkinin system been explored. Fifteen essential hypertensive white men were treated with both placebo and oral propranolol for 1 month each, with dosage titrated for blood pressure control. Propranolol normalized mean arterial pressure (from 112.6 ± 1.9 to 94.0 ± 2 . 8 m m H g , p < 0.01) with associated decrements in glomerular filtration (GFR) by 12% (p < 0.02), renal plasma flow (RPF) by 15% (p < 0.02), and renal blood flow (RBF) by 16% (p < 0.01), while filtration fraction was unchanged. Neither blood urea nitrogen nor serum creatinine were affected. Propranolol also diminished urinary kallikrein excretion (from 9.0 ± 2.7 down to 4.8 ± 1 . 3 esterase units/24 hrs, p < 0.04). Comparison to a group of 10 controls showed a progressive decrease in RBF from normotensive man, to hypertensive man, to propranolol-treated hypertensive man, with a parallel progressive fall in kallikrein excretion in the same three groups. Change in RBFon propranolol correlated inversely with pretreatment RBF (r = —0.91, p < 0.01) and pretreatment urinary catecholamine excretion (r = —0.64, p < 0.01), directly with pretreatment RVR (r = -0 .85 , p < 0.01) and inversely with change in RVR (r = -0.86, p < 0.01). This suggests that: 1) there was a failure of renal perfusion autoregulation; 2) a decrement in RBF was most likely to occur in patients with a relatively "normal" renal vascular tree; and 3) unopposed alpha mediated vasoconstriction was a likely mediator of the RBF fall. Change in RBF did not correlate with change in kallikrein excretion (r = —0.16), while change in kallikrein excretion correlated best with pretreatment kallikrein excretion (r = —0.87, p < 0.01), although not with change in plasma aldosterone concentration or urinary sodium/potassium ratio. Urinary sodium excretion was unimpaired on propranolol (160 ± 21 vs 173 ± 12mEg/24hrs,p> 0.1), even in the face of a diminished glomerular filtration rate, and was sustained by an increase in the fractional excretion of sodium (from 0.75 ± 0.09 to 0.96 ± 0.06%, p < 0.05). This is perhaps related to diminished mineralocorticoid activity as reflected by decreased plasma aldosterone concentration (from 68.4 ± 9.6 to 61.4 ± 16.1 pgAnl, p < 0.02), increased urinary sodium/potassium ratio (from 2.41 ± 0.33 to 3.12 ± 0.30, p < 0.01), and correlation between fractional sodium excretion increment with urinary sodium/potassium ratio increment (r = 0.82, p < 0.01). Preservation of sodium homeostasis was also indicated by constancy in body weight, plasma volume, and blood volume. Kallikrein changes did not correlate with changes in renal sodium handling. (Hypertension 4: 742-749, 1982)