Influence of AT1 receptor blockade on blood pressure, renal haemodynamics and hormonal responses to intravenous angiotensin II infusion in hypertensive patients.
The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean +/- SEM, 106 +/- 2 mmHg) was significantly decreased compared with treatment with losartan (110 +/- 2 mmHg) and valsartan (109 +/- 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 +/- 0.4%) significantly more than losartan (1.5 +/- 0.4%) and valsartan (1.6 +/- 0.4%) and reduced the increase in aldosterone secretion (17 +/- 5 pg/ml/) significantly more than losartan (74 +/- 17 pg/ml/) and valsartan (82 +/- 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT1 receptor blockade with candesartan.
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage* / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007262:Infusions, Intravenous; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D000068756:Valsartan; D012083:Renin; D014633:Valine; D019808:Losartan; C081643:candesartan