title: Disparate systemic and renal blocking properties of angiotensin II antagonists during exogenous angiotensin II administration: implications for treatment.
abstract: Generation of angiotensin II (Ang II) contributes to the pathogenesis of cardiovascular diseases. Owing to the existence of high levels of Ang II within the kidney, blockade of the intrarenal Ang II levels may be important since long term outcome seems not only to be related to blood pressure per se. This was a prospective, randomized, double-blind, placebo-controlled study, with crossover design. We examined in 13 patients with mild to moderate hypertension the specific systemic and renal blocking properties of two different Ang II receptor blockers during a wide range of Ang II concentrations, 24 h post dose. The effects were evaluated after 4 weeks treatment with candesartan cilexetil (16 mg OD), losartan (50 mg OD) and placebo using clearance techniques. Candesartan reduced the 24 h blood pressure better than losartan (138(*)/87+/-12/8 vs 145/89+/-12/7 mmHg, (*)P<0.05 vs losartan) and placebo. Despite the lower blood pressure, candesartan attenuated the Ang II-induced response on ERPF and RVR markedly better than losartan or placebo. The GFR decreased, as expected, with placebo, but remained stable with candesartan. The present study demonstrates that in hypertensive patients candesartan and to a lesser degree losartan are effective in blocking the systemic and renal effects of Ang II during a wide range of Ang II infusion rates. Interestingly, 24 h post dose, candesartan effectively diminished the change in ERPF as well as GFR. This sustained renal effect of candesartan may be of importance, especially in pathophysiological circumstances in which (high renal levels of) Ang II contributes to cardiovascular damage.
authors.affiliation: Department of Nephrology, University Medical Center, Utrecht, The Netherlands. jmrwillemsen@planet.nl
authors.forename: J M
authors.initials: JM
authors.lastname: Willemsen
authors.forename: T J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: P
authors.initials: P
authors.lastname: Boer
authors.forename: C A
authors.initials: CA
authors.lastname: Gaillard
mesh_terms: D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects*; D019808:Losartan / Q000627:therapeutic use*; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D012083:Renin; D019808:Losartan; C077793:candesartan cilexetil