title: Different effects of angiotensin receptor blockade on end-organ damage in salt-dependent and salt-independent hypertension.
abstract: BACKGROUND
  Although angiotensin II type 1 receptor blockers have emerged as effective antihypertensive agents, it is not known how efficacious these agents are in treating hypertension-associated target organ damage.
  
  
  RESULTS
  The present study was undertaken to compare the effect of angiotensin type 1 receptor inhibition on the progression of the organ damage observed in 2 models of hypertension, namely, salt-sensitive and nitric oxide synthase inhibition-mediated hypertension. Effective (16.4 micromol/kg) and ineffective (0.8 to 4.9 micromol/kg) antihypertensive doses of candesartan cilexetil were initiated after hypertension was established. Both low- and high-dose candesartan cilexetil significantly reduced cardiac and renal damage in the nitric oxide synthase inhibitor model of hypertension (P < 0.05 versus untreated); however, high-dose candesartan caused a significant increase in renal damage in the Dahl salt-sensitive model of hypertension (P < 0.05 versus untreated). Interestingly, the beneficial end-organ effects of candesartan in the nitric oxide synthase inhibition model were independent of sustained antihypertensive actions of candesartan, whereas the exacerbation of renal injury with candesartan in the Dahl salt-sensitive model was inversely related to its blood pressure-lowering effect.
  
  
  CONCLUSIONS
  These data show that angiotensin type 1 blockade reduces injury in the l-nitroarginine methyl ester model but increases tissue injury in the salt-sensitive model. These data suggest that angiotensin II via angiotensin type 1 receptor activation contributes to organ damage in nitric oxide-deficient salt-independent hypertension but is protective in salt-induced hypertension. These data further suggest that (1) renal injury may evolve independently of blood pressure and (2) the effectiveness of an antihypertensive agent in ameliorating renal injury may depend on the etiology of the hypertension.
authors.affiliation: Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass, USA.
authors.forename: Karlene
authors.initials: K
authors.lastname: Maitland
authors.forename: Lakeesha
authors.initials: L
authors.lastname: Bridges
authors.forename: Wendell P
authors.initials: WP
authors.lastname: Davis
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.forename: Mildred A
authors.initials: MA
authors.lastname: Pointer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018450:Disease Progression; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; C081643:candesartan