Exaggerated natriuresis after selective AT1 receptor blockade in Dahl salt-sensitive rats.
Salt-sensitive individuals are susceptible to develop hypertension when exposed to high salt-diet. Such a phenomenon is considered to be due to a genetic impairment in the renal excretion of sodium. In the present studies extent of endogenous angiotensin-II (Ang-II) mediated antinatriuresis was comparatively evaluated in Dahl salt-sensitive (SS) and salt-resistant (SR) rats, using a selective AT1 receptor antagonist, candesartan. In addition, differences in plasma renin activity and characteristics of Ang-II receptors in the renal cortical tubular membranes were also examined. Under INACTIN anesthesia AT1 receptor blockade resulted in significant increases in renal sodium excretion, which was several-fold greater in SS rats than that observed in SR rats. These observations suggest that antinatriuretic function of endogenous angiotensin-II is exaggerated in SS rats. This functional overexpression appears to be related to an increase in the affinity of Ang-II receptors in renal cortical tubular membranes but not to receptor density or plasma renin activity. It is proposed that salt-dependent hypertension in Dahl salt-sensitive rats may be due to enhanced Ang-II mediated sodium retention.
Tallam
L S
LS
Institute for Cardiovascular Studies, University of Houston, TX 77204-5515, USA.
Jandhyala
B S
BS
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1; D012083:Renin / Q000097:blood; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary; D013777:Tetrazoles; D012083:Renin; C081643:candesartan