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Verapamil‐induced natriuretic and diuretic effects: Dependency on sodium intake
Author(s) -
Hughes George S,
Cowart T D,
Oexmann Mary Joan,
Conradi Edward C
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.172
Subject(s) - verapamil , endocrinology , medicine , plasma renin activity , chemistry , diuretic , calcium , urine osmolality , urine sodium , sodium , urine , renin–angiotensin system , blood pressure , organic chemistry
The influence of dietary sodium on the antihypertensive effects of verapamil and on components of sodium, water, and calcium metabolism was studied in nine white patients 50 to 65 years old with normal renin hypertension. Diets consisting of 109 and 259 mEq Na were given for 5 days each before the study drug was given. On days 4 and 9, intravenous verapamil (0.075 mg/kg) and oral verapamil (80 mg) were given, followed by 80 mg at 8‐hour intervals for three doses. On days 1,4, 5, 9, and 10, serum and urine electrolytes, osmolality (urine [U osm ], serum [S osm ], and osmolar clearance [C osm ]), calcium plasma renin activity (PRA), and levels of serum aldosterone, 1,25‐hydroxyvitamin D, serum ionized calcium, parathyroid hormone, atrial natriuretic hormone (atriopeptin), and erythrocyte calcium and electrolytes were measured. On days 5 and 10, serial plasma samples for measurement of verapamil and norverapamil levels were drawn immediately after the last oral dose of verapamil. After verapamil, U osm and C osm decreased during both 109 and 259 mEq sodium diets (U osm , p < 0.025; C osm , p < 0.01 and p < 0.025, respectively), but free water clearance increased during each diet ( p < 0.01). Urine volume and sodium excretion increased with the 259 mEq sodium diet ( p < 0.025 and p < 0.01, respectively). There were no significant changes in measured values of components of calcium metabolism with either diet or after verapamil. The pharmacokinetics of verapamil were similar during each diet. Twenty‐four hours after the last oral dose of verapamil, supine mean arterial pressure (MAP) decreased ~5 mm Hg (109 mEq sodium diet; p < 0.025), whereas supine MAP declined ~10 mm Hg compared with baseline values during the 259 mEq sodium diet ( p < 0.01). Standing MAP declined by 8 mm Hg with either diet after verapamil ( p < 0.025 to p < 0.01). Thus the antihypertensive effects of verapamil are present regardless of sodium intake and are accompanied by natriuresis and diuresis during a high‐sodium diet. Clinical Pharmacology and Therapeutics (1988) 44, 400–407; doi: 10.1038/clpt.1988.172