Acute effects of combined vasodilation and beta‐adrenoceptor blockade with prizidilol on renal function.

Abstract

1 The effects of a single oral dose of 600 mg of prizidilol on renal function were studied 5 to 6 h after dosing in six normal subjects and eight patients with essential hypertension. 2 Mean arterial blood pressure was reduced to 92% of the control value in normal subjects and to 75% in hypertensive patients. Heart rate increased slightly. 3 In normal subjects, effective renal plasma flow was increased to 107% of control values while glomerular filtration rate (83%), filtration fraction (79%), sodium (84%) and potassium (50%) clearances were significantly decreased. 4 In hypertensive subjects, effective renal plasma flow was increased to 120% of control values, while glomerular filtration rate (67%), filtration fraction (57%), sodium (27%) and potassium (72%) clearances were significantly decreased. 5 Plasma noradrenaline increased significantly in normal subjects (150%) and in patients (173%).Plasma renin activity, aldosterone and epinephrine levels did not change consistently. 6 The results indicate that the acute effects of prizidilol on blood pressure and renal function are more marked in hypertensive than in normotensive subjects. Prizidilol increases renal plasma flow like hydralazine and depresses glomerular filtration rate and fractional sodium excretion like endralazine. In addition to the fall in arterial pressure, efferent vasodilation and/or a specific effect on the glomerular ultrafiltration coefficient Kf may account for the striking decrease in filtration fraction.

Effects of carvedilol on renal function

“…It is tempting to speculate that carvedilol, when given acutely, reduces the GFR by interfering with the compensatory autoregulatory constriction of the efferent arteriole, thus producing an acute decrease in glomerular perfusion pressure. It is noteworthy that prizidilol, a non-selective [3-blocker with vasodilating properties [30] that has been withdrawn from study because of side effects, has a definite renal vasodilatory effect and also reduces the GFR and FF after acute administration [31].…”

The effect of celiprolol on glomerular filtration rate and renal blood flow in patients with chronic renal impairment and healthy volunteers.

“…The nonselective 13-adrenoceptor blockers, propranolol (Danesh et al, 1984) and nadolol (O'Callaghan et al, 1983), have been reported to reduce ERBF during short term oral administration as has the vasodilator Padrenoceptor blocker, prizidolol (Andersen et al, 1985). Another study of nadolol showed a significant increase in ERBF (Boehringer et al, 1983). Acebutolol, timolol, penbutolol and bevantolol have been reported as having no significant effect on GFR or ERBF (Solimon et al, 1986;Valvo et al, 1984; Van der Meiracker et al, 1988; Van der Meulen et al, 1986).…”

Comparison of the effects of prizidilol and propranolol on renal haemodynamics at rest and during exercise.

“…The prizidilol induced increase in renal perfusion, which takes place without change in cardiac output and fluid volumes (Lund-Johansen & Omvik, 1982), can probably be attributed to a selective renal vasodilation which is maintained beyond the acute administration of the drug (Boehringer et al, 1983).…”

“…The drug, in the long term, induces a favourable haemodynamic pattern in that it lowers blood pressure levels without modifying heart rate and cardiac output both at rest and during exercise (Lund-Johansen & Omvik, 1982). On the other hand, the acute administration of the drug has been reported to increase renal perfusion, but to depress glomerular filtration rate (Boehringer et al, 1983 Titration was effected until normalization of BP (<95 mm Hg diastolic BP (Korotkoff phase 5) after 5-min lying) unless important side effects appeared or the ceiling dose of 480 mg/day of propranolol and 800 mg/day of prizidilol was reached.…”

“…The drug, in the long term, induces a favourable haemodynamic pattern in that it lowers blood pressure levels without modifying heart rate and cardiac output both at rest and during exercise (Lund-Johansen & Omvik, 1982). On the other hand, the acute administration of the drug has been reported to increase renal perfusion, but to depress glomerular filtration rate (Boehringer et al, 1983).…”