Is there a role for renal alpha 2-adrenoceptors in the pathogenesis of hypertension?
Current information suggests that alpha 2-adrenoceptors do not directly influence vascular resistance or Na reabsorption in the rat kidney. To reexamine the effects of alpha 2-agonists we used isolated rat kidneys perfused at 37.5 degrees C with precise measurement of renal artery pressure and flow. The recirculating perfusate contained pyruvate as the sole metabolic substrate which enabled us to use gluconeogenesis as an index of proximal tubular alpha 1-responses. Clonidine and guanfacine in 100 nM concentrations decreased phosphate excretion without altering Na, Cl, or K reabsorption or gluconeogenesis; 500 nM concentrations increased vascular resistance and decreased glomerular filtration rate and Na, Cl, and K excretion with no significant effect on gluconeogenesis. Prior thyroparathyroidectomy prevented the antiphosphaturic but not the antinatriuretic or vascular responses. Clonidine, an alpha 2-agonist with some alpha 1-activity, was a more potent vasoconstrictor than methoxamine or guanfacine. In the presence of prazosin (1 microM), norepinephrine (60 nM) stimulated phosphate reabsorption; norepinephrine alone did not stimulate phosphate reabsorption which indicates alpha 1-antagonism of this alpha 2-response to NE. These results and a literature review suggest that increased renal alpha 2-adrenoceptors could raise renal vascular resistance, reduce renin secretion, and antagonize parathyroid hormone effects on Pi, Ca, HCO3, and Na reabsorption to produce a low renin type of hypertension with increased proximal Na reabsorption and abnormal Ca and Pi excretion.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology*; D006973:Hypertension / Q000209:etiology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000502:physiology; D010648:Phenylacetates / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D006146:Guanidines; D010648:Phenylacetates; D011773:Pyruvates; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D016316:Guanfacine; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin