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Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients
Insights
Essential hypertension is linked to impaired nitric oxide production. This study in offspring suggests a nitric oxide pathway defect precedes high blood pressure development.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Hypertension Research
Background:
- Essential hypertension is associated with impaired endothelium-dependent vasodilation.
- The study investigates if this vasodilation defect is primary or secondary to elevated blood pressure.
Purpose of the Study:
- To determine if offspring of essential hypertensive patients exhibit impaired endothelium-dependent vasodilation.
- To investigate the role of the nitric oxide pathway in this potential abnormality.
Main Methods:
- Forearm blood flow was measured using strain-gauge plethysmography in offspring of hypertensive and normotensive subjects.
- Vascular responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) were assessed.
- The effect of L-arginine and indomethacin on acetylcholine-induced vasodilation was evaluated.
Main Results:
- Offspring of hypertensive patients showed significantly blunted vasodilation to acetylcholine compared to controls.
- Responses to sodium nitroprusside and minimal forearm vascular resistance were similar between groups.
- L-arginine partially restored acetylcholine-induced vasodilation in hypertensive offspring, while indomethacin had no effect.
Conclusions:
- Offspring of essential hypertensive patients have a reduced vasodilatory response linked to a nitric oxide pathway defect.
- This impairment in nitric oxide production appears to precede the clinical onset of essential hypertension.
- Findings suggest a primary defect in endothelial function may contribute to hypertension development.
Background:
Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to investigate whether this abnormality is a primary defect or a consequence of blood pressure increases.
Methods And Results:
In offspring of essential hypertensive patients (n = 34) and normotensive subjects (n = 30), we evaluated forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator. Minimal forearm vascular resistances also were calculated as the ratio between mean intra-arterial pressure and maximal forearm blood flow induced by forearm ischemia and hand exercise. Vasodilation to acetylcholine was significantly (P < .01) blunted in offspring of hypertensive patients compared with offspring of normotensive subjects, whereas the responses to sodium nitroprusside and minimal forearm vascular resistances were similar. In two subgroups of 14 offspring of essential hypertensive patients but not in 10 offspring of normotensive subjects, vasodilation to acetylcholine was increased by intra-brachial L-arginine (1 mumol.100 mL-1.min-1), the substrate for nitric oxide synthesis, whereas in the other 10 and 8 offspring of essential hypertensive patients and normotensive subjects, respectively, cyclooxygenase blockade by intra-brachial indomethacin (50 micrograms.100 mL-1.min-1) was ineffective.
Conclusions:
Offspring of essential hypertensive patients are characterized by a reduced response to acetylcholine linked to a defect in the nitric oxide pathway, suggesting that an impairment in nitric oxide production precedes the onset of essential hypertension.