Delineation of the site of action of guanabenz in the renal tubule.
Guanabenz, a centrally acting alpha 2-agonist, has been shown to lower blood pressure (BP) while maintaining glomerular filtration rate and increasing water and solute excretion. The site and mechanism of the increased solute excretion are still unclear. To evaluate the effect of guanabenz on water and solute reabsorption in the collecting duct, Munich Wistar rats were utilized in micropuncture experiments. Micropuncture samples were obtained from the most proximal portion (base) of the collecting duct and the most distal part (tip). In an initial group of hydropenic rats, collecting duct water and chloride (Cl) reabsorption were evaluated during a control and experimental period during which guanabenz was infused at 20-40 micrograms/kg/min. Although the mean drop in BP was 18 mm Hg after guanabenz infusion, at any given rate of Cl delivery, the reabsorption was less than that for the control period. Another group of studies utilizing the plasma repletion method to increase Cl excretion was used to evaluate collecting duct reabsorption. BP was lowered in rats by an aortic snare to approximately 95 mm Hg and papillary collecting duct (PCD) samples were obtained. The snare was then released and 100-400 micrograms/kg/min of guanabenz was infused and the rate adjusted to produce a drop in BP similar to that of the initial period. During the control period, PCD fluid to plasma inulin ratios were 23.1 +/- 4.3 and 37.3 +/- 4.6 at the base and tip, respectively. This ratio was decreased to 10.9 +/- 3.1 and 15.7 +/- 4.6 at the base and tip puncture sites, respectively, during guanabenz infusion. PCD chloride reabsorption during the initial period was 40.3% +/- 7.0% of the load delivered. During the guanabenz infusion, however, only 12.8% +/- 3.4% of the delivered load was reabsorbed (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D006143:Guanabenz / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007679:Kidney Medulla / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014882:Water-Electrolyte Balance / Q000187:drug effects
D006146:Guanidines; D006143:Guanabenz