Effects of angiotensin II and losartan in the forearm of patients with essential hypertension.
OBJECTIVE
Angiotensin II type 1 receptor-mediated constrictor effects may be modulated by hypertension-related vascular changes, changes in receptor function and in neurohumoral activity.


METHODS
The forearm blood flow (FBF) effects of angiotensin II, methoxamine, and losartan were investigated in essential hypertensive patients. Minimal forearm vascular resistance was measured to determine structural vascular changes.


METHODS
Seven hypertensive patients were selected, and seven matched normotensives. Angiotensin II (0.01-10 ng/kg per min) was infused during predilatation by sodium nitroprusside (6.1 +/- 0.6 ng/kg per min) before and during losartan infusion (0.3-3 microg/kg per min). Methoxamine (0.2-2 microg/kg per min) was co-infused with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. FBF, measured by venous occlusion plethysmography, was expressed as the change in FBF ratio (FBFinfused arm/FBFnon-infused arm).


RESULTS
Baseline FBF (infused arm) was increased by sodium nitroprusside from 2.56 +/- 0.80 to 5.46 +/- 0.92 (P<0.05) and from 2.66 +/- 0.25 to 5.42 +/- 0.40 ml/100 ml per min (P<0.05) in the hypertensive and normotensive group, respectively. Baseline forearm vascular resistance (FVR) was higher in the hypertensive than in the normotensive group [51 +/- 8 versus 33 +/- 3 mmHg/ (ml/100 ml per min); P<0.05]. Angiotensin II caused a maximal change in FBF ratio (Emax) by -70 +/- 3 and -72 +/- 6% in the hypertensive and normotensive group, respectively (NS). Tachyphylaxis did not occur. Infusions of losartan at 0.3, 1 and 3 microg/kg per min reduced the Emax values from -70 +/- 3 to -50 +/- 5, -45 +/- 5 and -15 +/- 2%, respectively, in the hypertensive group, and from -72 +/- 6 to -62 +/- 4, -45 +/- 2 and -32 +/- 2%, respectively, in the normotensive group (NS). Infusion of methoxamine significantly reduced the FBF ratio by -58 +/- 6 and -69 +/- 5% in the hypertensive and normotensive groups, respectively (NS). Minimal FVR, after forearm ischemia, was the same in hypertensives and normotensives, namely 3.2 +/- 0.7 and 3.2 +/- 0.4 mmHg/(ml per 100 ml per min), respectively (NS).


CONCLUSIONS
Angiotensin II type 1- and alpha1-mediated vascular effects were unchanged by essential hypertension. Baseline FVR was greater in the hypertensives than in the normotensives, while minimal FVR was the same. These results indicate that the forearm vascular bed of the patient group studied does not show important structural and renin-angiotensin system-related functional changes as a result of hypertension.
Baan
J
J
Department of Nephrology, Leiden University Medical Centre, The Netherlands. J.Baan@AMC.UVA.NL
Chang
P C
PC
Vermeij
P
P
Pfaffendorf
M
M
van Zwieten
P A
PA
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D008729:Methoxamine; D019808:Losartan