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      Changes in Renal and Systemic Hemodynamics after NO-Synthase Inhibition in Males with Family History of Hypertension

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          Background: Nitric oxide (NO) plays an important role in the regulation of blood pressure and renal hemodynamics. Methods: To further investigate the role of NO in human hypertension, we studied the effect of systemic injection of N<sup>G</sup>-monomethyl- L-arginine (L-NMMA) on renal hemodynamics, urinary sodium excretion (FE<sub>Na</sub>), systemic hemodynamics and several vasoactive hormones in 5 healthy male subjects with (group H) and without (group N) family history of hypertension. An intravenous infusion of L-NMMA (3 mg/kg over 10 min) or placebo was given in a randomized, double-blinded manner. GFR and ERPF were measured by inulin- and PAH-clearances. Norepinephrine infusion (0.1 µg/kg/min over 60 min) served as vasoconstrictive control infusion. Results: L-NMMA induced a significant decrease in ERPF (–135 ± 49 vs. 7 ± 31 ml/min/1.73 m<sup>2</sup> with placebo, p < 0.05), a decrease in FE<sub>Na</sub> (–1.2 ± 0.6% with L-NMMA vs. 0.0 ± 0.1% with placebo), and a significant increase in diastolic blood pressure (+7 ± 1 vs. –2 ± 1 mm Hg with placebo) in group N, only. A sustained drop in plasma renin activity (–0.1 ± 0.1 vs. 0.3 ± 0.1 ng/ml/h with placebo) could also be seen in this group, only. Subjects with family history of hypertension showed minor or even no response (changes in diastolic blood pressure: L-NMMA: 5 ± 3 mm Hg, placebo: 0 ± 2 mm Hg; changes in ERPF: L-NMMA: –89 ± 57 ml/min/1.73 m<sup>2</sup>, placebo: –34 ± 28 ml/min/1.73 m<sup>2</sup>; changes in plasma renin activity: L-NMMA: –0.0 ± 0.3 ng/ml/h, placebo: –0.1 ± 0.2 ng/ml/h). The vasoconstrictive effect of norepinephrine infusion did not differ between both groups. Conclusion: Our data indicate that systemic NO synthetase inhibition by L-NMMA results in a blunted effect on systemic blood pressure and the renal hemodynamic system in subjects with family history of hypertension.

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          Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia.

          Endothelium-dependent vasodilation in response to acetylcholine is impaired in the coronary microvasculature of hypercholesterolaemic subjects. Outside the coronary circulation, however, it has been suggested that hypercholesterolaemia results in a functional abnormality of vascular smooth muscle rather than in endothelial dysfunction. We examined vasodilator responses to acetylcholine, methacholine, and the endothelium-independent vasodilator sodium nitroprusside in the forearm resistance vessels of 12 men with primary hypercholesterolaemia and 12 normocholesterolaemic male controls. Endothelium-dependent vasodilation in response to acetylcholine was impaired in hypercholesterolaemic patients compared with controls: at the highest dose of drug (15 micrograms per min) mean blood flow in the forearms of the hypercholesterolaemic group was only 52% (95% Cl 31-88%) of that in the control group. Responses to sodium nitroprusside and to methacholine in the two study groups were not significantly different. These results indicate that endothelial dysfunction in hypercholesterolaemic subjects is generalised and extends to vascular beds outside the coronary circulation. Selective impairment to acetylcholine suggests that, at a molecular level, the defect is limited to a specific pathway.
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            Impairment of endothelial function in salt-sensitive hypertension in humans.

            In this study, we evaluated the relationship between the endothelium-dependent vasodilation and salt sensitivity in patients with essential hypertension. Fifteen untreated hypertensive male patients (age, 29 to 54 years) were sodium restricted (5 g/day) for 1 week, and placed on a high salt diet (20 g/day) the second week. At the end of each period, measurements of forearm vascular responses to drugs (acetylcholine, 3 to 24 microg/min; sodium nitroprusside, 0.15 to 1.2 microg/min; norepinephrine, 0.15 to 1.2 microg/min; and N(G)-monomethyl-L-arginine [L-NMMA], 1 to 8 micromol/min) were obtained by using strain-gauge venous plethysmography. Subjects were divided into two groups according to the blood pressure response to sodium loading: salt-sensitive hypertensive group (24-h mean increase of arterial pressure > or = 10%; n = 6) and salt-resistant group (< 10%; n = 9). The two groups showed no significant difference in clinical data or mean arterial pressure during low salt intake. The dose-dependent vasodilation induced by acetylcholine was significantly reduced (P < .05) in the salt-sensitive hypertensive patients v the salt-resistant patients regardless of sodium loading. There were no differences between the two groups in response to sodium nitroprusside, norepinephrine, or L-NMMA. These results indicate that vasodilation to acetylcholine is reduced in salt-sensitive hypertensive patients even on restricted sodium diets. This may contribute to blood pressure elevation when sodium intake is increased.

              Author and article information

              Kidney Blood Press Res
              Kidney and Blood Pressure Research
              S. Karger AG
              06 February 2002
              : 25
              : 1
              : 42-49
              University of Tübingen, Department of Internal Medicine III, Eberhard Karls University, Tübingen, Germany
              49434 Kidney Blood Press Res 2002;25:42–49
              © 2002 S. Karger AG, Basel

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              Figures: 3, Tables: 3, References: 28, Pages: 8
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