Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been proposed repeatedly that essential hypertension as well as secondary hypertension is associated in a causative manner with endothelial dysfunction in the resistance vessels. Endothelial damage and dysfunction may be expected to attenuate the endogenous vasodilator mechanism of EDRF (nitric oxide) and hence cause a rise in blood pressure. This attractive hypothesis, put forward a few years ago, is subject to considerable debate at present. In the present survey the arguments in favour and against this hypothesis are critically discussed. The following arguments support the causative association between endothelial dysfunction: the hypertensive effect of NO-synthase blockade by L-NAME and related agents; the antihypertensive effect of L-arginine in salt-loaded Dahl rats; the impaired vasodilator effect in the forearm vascular bed of hypertensives; diminished NO-synthesis in hypertensives. However, several findings speak against the association between hypertensive disease and endothelial dysfunction. For instance: no clear demonstration of impaired endothelial function in isolated vessels of hypertensive patients and animals; studies in the human forearm vascular bed where endothelial function appears to be fully intact in hypertensives. Attempts are made to explain the discrepancies between the various findings. So far the association between endothelial dysfunction and hypertension appears to be an uncertain one.
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PMID:Endothelial dysfunction in hypertension. A critical evaluation. 949 30

We developed mice deficient in protease-activated receptor-2 (PAR-2) or PAR-1 to explore the pathophysiological functions of these receptors. In this report, we evaluated mean arterial pressure and heart rate (HR) changes in response to PAR-1 or PAR-2 activation in anesthetized wild-type (WT), PAR-1-deficient (PAR-1(-/-)), and PAR-2-deficient (PAR-2(-/-)) mice. In WT mice, TFLLRNPNDK, a PAR-1 selective activating peptide, caused hypotension and HR decreases at 1 micromol/kg. TFLLRNPNDK also caused secondary hypertension following L-NAME pretreatment. These responses were absent in PAR-1(-/-) mice. In WT mice, SLIGRL, a PAR-2 selective activating peptide, caused hypotension without changing HR at 0.3 micromol/kg. SLIGRL did not induce hypertension following Nomega-nitrol-arginine-methyl ester-HCl (L-NAME). The response to SLIGRL was absent in PAR-2(-/-) mice. SFLLRN, a nonselective receptor activating peptide caused hypotension and HR decreases in WT mice at 0.3 micromol/kg, as well as secondary hypertension following L-NAME. SFLLRN still induced hypotension in PAR-1(-/-) mice, but HR decrease and secondary hypertension following L-NAME were absent. The hypotensive and bradycardic responses to SFLLRN and TFLLRNPNDK in PAR-2(-/-) mice were accentuated compared with WT mice. By using mouse strains deficient in either PAR-1 or PAR-2, we confirmed the in vivo specificity of TFLLRNPNDK and SLIGRL as respective activating peptides for PAR-1 and PAR-2, and the distinct hemodynamic responses mediated by activation of PAR-1 or PAR-2. Moreover, the accentuated response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory response and potential receptor cross-talk.
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PMID:Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1. 991 74

In spontaneously hypertensive rats, ouabain exerts an excitatory effect on baroreceptor nerve activity (BNA). The aim of this study was to determine the effects of ouabain on BNA in other experimental models of hypertension and its interaction with nitric oxide. Rats were made hypertensive using the procedures for N(omega)-nitro-L-arginine methyl ester (L-NAME), deoxycorticosterone acetate (DOCA) salt, and 2-kidney, 1 clip (2K1C) hypertension models. In these groups, systolic arterial pressure was 195+/-7, 149+/-6, and 148+/-4 mm Hg, respectively, compared with 110+/-4 mm Hg in normotensive rats. Acute ouabain administration had an excitatory effect on BNA in normotensive rats (37+/-4%), an inhibitory effect in L-NAME hypertensive rats (-60+/-7%), and no effect in DOCA-salt and 2K1C hypertensive rats. The effects of ouabain were not related to arterial pressure levels, and no excitatory effect on BNA was observed in prehypertensive DOCA-salt rats. Long-term administration of L-arginine (3 g x kg(-1) x day(-1)) prevented DOCA-salt (121+/-8 mm Hg) and 2K1C (104+/-4 mm Hg) hypertension, markedly attenuated L-NAME (130+/-9 mm Hg) hypertension, and restored the excitatory effect of ouabain on BNA in these groups to levels similar to the normotensive rats and their respective control groups. We conclude that ouabain has a diverse effect on BNA in experimental models of hypertension, and it can be normalized by L-arginine. The data also indicate that nitric oxide may play a pivotal role in mediating the excitatory effect of ouabain on BNA, and we speculate that a therapeutic combination of ouabain and L-arginine may be beneficial in secondary hypertension.
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PMID:L-arginine restores the effect of ouabain on baroreceptor activity and prevents hypertension. 1052 50

Changes in the lipid composition of the membrane affect its fluidity and function. These variables are altered in various forms of hypertension. Our hypothesis was that the rapid increase in blood pressure (BP) caused by inhibition of nitric oxide production would lead to alterations in membrane fluidity similar to those observed in genetic hypertension. We used Nomega-nitro L-arginine methyl ester (L-NAME) and vehicle-treated (3 weeks) Wistar-Kyoto rats to study the effects of nitric oxide synthase (NOS) inhibition on membrane fluidity and lipid composition. Erythrocyte membrane fluidity was measured by fluorescence anisotropy. Membrane lipids were separated using Sep-Pak and thin-layer chromatography. Fatty acid methyl esters were produced and analyzed by gas chromatography-mass spectrometry. Nomega-nitro L-arginine methyl ester treatment increased BP and erythrocyte membrane fluidity. The phospholipid and unsaturated fatty acid levels in the membranes from the L-NAME-treated rats were consistent with the increase in fluidity (ie, more unsaturated fatty acid, in particular, arachidonic and docosahexaenoic acid) and a reduction in membrane sphingomyelin content. Fatty acid analysis of individual lipid groups suggested the changes in membrane fatty acid composition may be asymmetric, with the majority of the changes occurring in the outer leaflet. Inhibition of NOS results in changes in membrane composition that may explain the concurrent changes in fluidity. The increased membrane fluidity observed here contrasts with the reduced fluidity observed in genetic hypertension or unchanged fluidity in secondary hypertension. The effects could be related to NOS inhibition or may be a direct effect of L-NAME.
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PMID:Inhibition of nitric oxide synthesis increases erythrocyte membrane fluidity and unsaturated fatty acid content. 1107 80