Noradrenergic vascular hyper-responsiveness in human hypertension is dependent on oxygen free radical impairment of nitric oxide activity.
نویسندگان
چکیده
BACKGROUND Noradrenergic vascular hyper-responsiveness is a hallmark of essential hypertension. To evaluate whether nitric oxide plays a role in the enhanced vascular response to norepinephrine in hypertension, we examined 32 hypertensives and 28 normotensives who were distributed in 3 experimental series. METHODS AND RESULTS In the first series, we measured the forearm blood flow (FBF) response to a norepinephrine infusion under control conditions and during the infusion of L-N-monomethylarginine (L-NMMA). Norepinephrine evoked dose-dependent vasoconstriction that was greater in hypertensives than in normotensives (maximum FBF, -61+/-1 versus -51+/-1%; P<0.01). During L-NMMA infusion, norepinephrine vasoconstriction was not modified in hypertensives; however, it was potentiated in normotensives (maximum FBF, -64+/-2%; P<0.01). In the second series, we tested whether norepinephrine vasoconstriction could be affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction was blunted by ascorbic acid administration only in hypertensives (maximum FBF, -49+/-3 versus -63+/-2%; P<0.01); the vasoconstriction became similar to that observed in normotensives. During ascorbic acid plus L-NMMA administration, the vascular response to norepinephrine increased to a similar extent in both study groups. To rule out the possibility that the effect of ascorbic acid on norepinephrine vasoconstriction could depend on adrenergic receptor-induced nitric oxide release, in the last series we inhibited endogenous nitric oxide and replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only in hypertensives (maximum FBF, -50+/-2 versus -62+/-1%; P<0.01). CONCLUSIONS Our data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension is dependent on an impairment of nitric oxide activity that is realized through norepinephrine-induced oxygen free radical production.
منابع مشابه
Oxygen Free Radical Impairment of Nitric Oxide Activity Noradrenergic Vascular Hyper-Responsiveness in Human Hypertension Is Dependent on
Giuseppe Lembo, Carmine Vecchione, Raffaele Izzo, Luigi Fratta, Dario Fontana, Gennaro Oxygen Free Radical Impairment of Nitric Oxide Activity Noradrenergic Vascular Hyper-Responsiveness in Human Hypertension Is Dependent on Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2000 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Gr...
متن کاملNoradrenergic cell specific gene transfer with neuronal nitric oxide synthase reduces cardiac sympathetic neurotransmission in hypertensive rats.
Nitric oxide-cGMP pathway can inhibit cardiac norepinephrine (NE) release. Sympathetic hyper-responsiveness in hypertension may result from oxidative stress impairing this pathway. We tested the hypothesis that the gene transfer of neuronal NO synthase (nNOS) could restore sympathetic balance in the spontaneously hypertensive rat (SHR). An adenovirus (5x10(10) particles) constructed with a nora...
متن کاملAntioxidant and Free Radical Scavenging Activities of Ervatamia coronaria Stapf. Leaves
The present study was carried out to evaluate the antioxidant and free radical scavenging activity of methanolic extract of Ervatamia coronaria leaves (Apocynaceae) in various systems. DPPH radical, superoxide anion radical, nitric oxide radical and hydroxyl radical scavenging assays were carried out to evaluate the antioxidant potential of the extract. The antioxidant activity of methanolic ex...
متن کاملAntioxidant and Free Radical Scavenging Activities of Ervatamia coronaria Stapf. Leaves
The present study was carried out to evaluate the antioxidant and free radical scavenging activity of methanolic extract of Ervatamia coronaria leaves (Apocynaceae) in various systems. DPPH radical, superoxide anion radical, nitric oxide radical and hydroxyl radical scavenging assays were carried out to evaluate the antioxidant potential of the extract. The antioxidant activity of methanolic ex...
متن کاملNitric oxide and the bioactivities
Nitric oxide (NO), previously known as Endothelium-Derived Relaxing Factor (EDRF) is involved in a wide range of physiological and pathophysiological mechanisms. It is synthesized endogenously by the enzymes Nitric Oxide Synthase (NOS) in specialized tissues from its precursor L-arginine, yielding L-citrulline as a byproduct. It is released by a family of isoenzymes, viz., the endothelial (eNOS...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation
دوره 102 5 شماره
صفحات -
تاریخ انتشار 2000