Abstract

Guanethidine was given i.v. and directly into the left renal artery of the dog, in an attempt to separate the systemic effects of this drug from its direct renal effects. The drug was given alone and after alpha adrenergic blockade with phenoxybenzamine. Intravenous injections of guanethidine (15 mg/kg) resulted in an increased urine flow, osmolar clearance and saluresis. There was a less marked increase in potassium excretion and no significant change in glomerular filtration rate or effective renal plasma flow (ERPF). The mean systemic blood pressure increased approximately 40 mm Hg. After phenoxybenzamine pretreatment, i.v. guanethidine did not produce significant saluresis or diuresis; there was, however, a consistent increase in ERPF. Guanethidine infused directly (left renal artery) at 1.5 to 3.0 mg/min resulted in a dose-related, unilateral increase in sodium, chloride, calcium, potassium and water excretion but no significant change in ERPF in spite of an increased mean blood pressure. Direct guanethidine infusion (left renal artery), after pretreatment with 5 mg/kg i.v. of phenoxybenzamine, still produced unilateral saluresis and diuresis although the magnitudes were reduced. The mean blood pressure was reduced or not changed. There was a significant increase in the tubular rejection fraction of sodium but no significant change in glomerular filtration rate or ERPF. In conclusion, guanethidine-induced saluresis appears to be the result of an increased tubular rejection of sodium directly within the kidney through its sympathetic blockade of renal nerves.