Guanabenz action on renal excretory function in New Zealand genetically hypertensive rats

The renal action of guanabenz, a centrally acting antihypertensive drug, was evaluated in anesthetized New Zealand genetically hypertensive rats and in normotensive Sprague-Dawley rats using clearance techniques. In high doses (1 mg/kg/hr), the drug lowered systemic blood pressure in the hypertensive rats without reducing glomerular filtration rate. Mean urine flow increased from 2.42 +/- 0.34 to 36.52 +/- 4.52 microliters/min per 100 g b.wt. while fractional water excretion increased from 0.34 +/- 0.05 to 4.36 +/- 0.50%. The renal and hemodynamic actions of the drug were sustained throughout the experiment. In a lower dose (10 micrograms/kg/hr), guanabenz reduced blood pressure in the hypertensive rats to an extent similar to that of the higher dose but had only a moderate effect on kidney function. Renal elimination of water, sodium and potassium increased slightly and glomerular filtration rate remained unchanged. Infusion of the vehicle alone did not cause significant changes in the hemodynamic and renal excretory functions. In the normotensive rats, receiving the high dose of the drug, mean urine osmolarity declined nearly 10-fold from 2466 +/- 136 to 290 +/- 37 mOsl while total solute excretion doubled. Infusion of the vehicle alone did not cause significant changes in the hemodynamic and renal excretory functions. The drug appears to have a primary action on the renal tubular handling of water and sodium. It may inhibit the secretion of antidiuretic hormone or block the antidiuretic hormone-stimulated cAMP-dependent increase in water permeability of the collecting tubules through its alpha 2-adrenoceptor agonistic effect. Natriuresis may have resulted in part from a lowered sympathetic tone to the kidneys.