Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To better define the time course of skeletal muscle glucose uptake and its modulation by changes in perfusion, we performed systemic euglycemic-hyperinsulinemic clamps (40 mU.m-2.min-1) for a 90-min period in a group of lean, insulin-sensitive subjects (n = 9) on two occasions (approximately 4 wk apart) with insulin-mediated vasodilation intact or inhibited. Insulin-mediated vasodilation was inhibited by an intrafemoral artery infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the study, leg blood flow (LBF) and arteriovenous glucose difference (AVG delta) were measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVG delta. The systemic insulin infusion caused a time-dependent increase in LBF from 0.194 +/- 0.024 to 0.349 +/- 0.046 l/min (P < 0.01). The intrafemoral artery infusion of L-NMMA completely inhibited this increase in LBF. AVG delta, LGU, and whole body glucose disposal rates increased in a time-dependent manner in both studies. The maximum AVG delta was lower with insulin-mediated vasodilation intact than when inhibited (25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl, P < 0.001). The time to achieve half-maximal (T1/2) AVG delta was somewhat longer with insulin-mediated vasodilation intact compared with inhibited (35.6 +/- 4.1 vs. 29.7 +/- 1.6 min, P < 0.01). Maximal LGU was 93.9 +/- 26.8 and 57.2 +/- 11.6 mg/min (P < 0.005), and the T1/2 LGU was 50.2 +/- 16.0 and 36.3 +/- 8.8 min (P = 0.1) during intact and inhibited insulin-mediated vasodilation, respectively. Thus insulin-mediated vasodilation has a modest effect in slowing the time course at which insulin stimulates glucose uptake but has a marked effect in augmenting the maximal rate of insulin-stimulated glucose uptake in skeletal muscle. Impaired insulin-mediated vasodilation, as observed in patients with essential hypertension, may explain, at least in part, the insulin resistance observed in these patients.
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PMID:Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake. 899 27

A putative pathogenic mutation in the beta3-adrenergic receptor gene (Trp64Arg) has been reported to be associated with higher diastolic blood pressure as well as clinical features of the insulin resistance syndrome and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians and Finns. Because essential hypertension is reported to be associated with insulin resistance, we studied the mutation in Japanese patients with essential hypertension to clarify associations of this mutation with hypertension, insulin resistance, and basal adrenergic state in hypertensive subjects. The allele frequency of the mutation (Arg) in patients with essential hypertension was similar to that in control subjects (35 of 202 alleles [17.3%] v 27 of 146 [18.5%], respectively, P > .7). Insulin sensitivity measured by hyperinsulinemic euglycemic glucose clamp and plasma norepinephrine and epinephrine levels were also similar in hypertensive subjects with and without the mutation. These data suggest that Trp64Arg mutation in the beta3-adrenergic receptor gene does not play a major role in susceptibility to essential hypertension or in insulin resistance and basal adrenergic state in hypertension.
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PMID:Trp64Arg mutation of beta3-adrenergic receptor in essential hypertension: insulin resistance and the adrenergic system. 900 54

The acute administration of nitric oxide (NO) synthesis inhibitors reduces the renal capacity to excrete sodium under normal or volume expanded conditions and increases renovascular resistances in the absence of changes in systemic blood pressure (BP). This indicates a sensitivity of renal vasculature higher than that of systemic vessels to NO synthesis inhibition. Medullary circulation is the renovascular territory most dependent on NO availability. Thus, alterations in medullary blood flow seems to account for the blunted pressure-natriuresis and sodium retention during acute NO synthesis inhibition. By contrast, during chronic administration of L-arginine analogs, systemic BP rises and overrides initial sodium retention by a resetting of the pressure-natriuresis relationship. This BP increase appears to be dependent on an overexpression of the actions of vasoconstrictor systems due to an imbalance created by the diminished NO production. Prolonged NO synthesis inhibition not only elevates BP, but also produces renal vascular and parenchymal damage. Antihypertensive therapy impedes BP elevation and ameliorates kidney deterioration. Finally, there is evidence of the possibility that a certain alteration in the L-arginine-NO pathway exists in genetic models and in human essential hypertension. In conclusion, according to the data contained in the literature, NO plays a significant role in the regulation of systemic and renal hemodynamics and excretory function, and could participate in the development of hypertension.
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PMID:Nitric oxide, the kidney, and hypertension. 900 58

Alterations in Ca2+ homeostasis have been proposed to be a primary factor in the pathogenesis of essential hypertension. In this disease increased intracellular Ca2+ levels have repeatedly been reported in various cell types. Because of its prominent role in cellular calcium homeostasis in vascular smooth muscle cells, modifications of the plasma membrane Ca2+-ATPase (PMCA) pump have been suggested to contribute to an increased contractile tone of small blood vessels. This pump is a calmodulin-dependent Ca2+-ATPase that ejects Ca2+ from the cytosol into the extracellular space. Recently a mutational thymidine (T)-->guanosine (G) transversion in isoform 1 of the PMCA has been identified resulting in the substitution of a methionine (Met) by an arginine (Arg) at amino acid position 267 in a highly conserved domain of the pump molecule. The aim of our study was to determine the prevalence of this polymorphism in the normal population and to investigate whether the Met-267 Arg occurs more frequently in patients with essential hypertension than in normotensives. To detect the mutational change we modified a method based on the technique of amplification-created restriction sites (ACRS) using three base exchanges in the diagnostic primer. Samples from 100 hypertensive and 60 normotensive subjects revealed a thymidine at nucleotide position 981. These data suggest that ACRS is feasible in spite of extensive primer modifications (e.g., three mismatched bases) in contrast to the previously used one or two and may therefore be conceptually suitable to detect almost any base changes in the genome. The described T-->G transversion is a rare polymorphism and is presumably not related to common forms of essential hypertension.
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PMID:Investigation of the Met-267 Arg exchange in isoform 1 of the human plasma membrane calcium pump in patients with essential hypertension by the amplification-created restriction site technique. 902 Mar 86

To evaluate whether cyclooxygenase constrictor substances can impair nitric oxide-mediated vasodilation in essential hypertension, in seven normotensive subjects (43.3 +/- 4.1 years; BP, 117 +/- 6/81 +/- 2 mm Hg) and seven essential hypertensive patients (47.1 +/- 5.2 years; BP, 151 +/- 8/98 +/- 4 mm Hg) we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 15 micrograms.100 mL-1.min-1) in basal conditions, during infusion of NG-monomethyl-L-arginine (L-NMMA; 100 micrograms.100 mL-1.min-1), a nitirc oxide synthase inhibitor, or indomethacin (50 micrograms.100 mL-1.min-1), a cyclooxygenase inhibitor, or simultaneous indomethacin and L-NMMA. In normotensives, vasodilation to acetylcholine was blunted by L-NMMA (maximum flow increase: 671 +/- 64% and 386 +/- 42%, respectively; P < .01), and this effect was unchanged by indomethacin. In contrast, in hypertensive patients, vasodilation to acetylcholine (maximum flow increase: 458 +/- 33%) was unchanged by L-NMMA. Indomethacin significantly (P < .01) increased the response to acetylcholine (maximum flow increase: 635 +/- 53%) and restored the inhibitory effect of L-NMMA (maximum flow increase: 445 +/- 36%; P < .01 versus indomethacin alone). In an adjunctive seven normotensives (51.4 +/- 4.2 years; BP, 114 +/- 5/79 +/- 3 mm Hg) and seven essential hypertensives (53.2 +/- 7.6 years; BP, 153 +/- 9/100 +/- 3 mm Hg) we repeated the same protocol by replacing L-NMMA with L-arginine (200 micrograms.100 mL-1.min-1), the substrate for NO synthase. In normotensives, vasodilation to acetylcholine was increased by L-arginine (maximum flow increase: 539 +/- 48% and 806 +/- 61%, respectively) and this effect was unchanged by indomethacin. In hypertensive patients, vasodilation to acetylcholine (maximum flow increase: 339 +/- 32%) was unchanged by L-arginine but was significantly (P < .01) increased by indomethacin (maximum flow increase: 592 +/- 38%). Moreover, indomethacin restored the facilitatory effect of L-arginine (maximum flow increase: 804 +/- 56%; P < .01 versus indomethacin alone). Therefore, cyclooxygenase inhibition restores nitric oxide-mediated vasodilation in essential hypertension, suggesting that cyclooxygenase-dependent substances can impair nitric oxide production.
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PMID:Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension. 903 14

The infusion of L-arginine induces the production of nitric oxide and stimulates the immediate secretion of insulin. To examine the relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension, we evaluated the renal and insulin responses to L-arginine, 500 mg/kg infused intravenously over 30 minutes, in 23 patients with mild essential hypertension who were neither obese nor diabetic and in 20 normotensive control subjects. We found no difference between the two groups in blood glucose or insulin in the fasting condition. The renovascular relaxation induced by L-arginine was significantly less in patients with essential hypertension than in normotensive control subjects. The increase in plasma cyclic GMP in response to L-arginine was lower in hypertensive patients than in normotensive subjects. Although the serum concentrations of glucose in response to L-arginine were similar in the two groups, the serum insulin response of the essential hypertensives was significantly higher than that of the normotensive subjects. In all subjects, the peak cyclic GMP response to L-arginine was significantly correlated with the peak delta glucose/ delta insulin ratio response to L-arginine (r = .69, P < .001). Findings suggested that an impairment of endothelium-dependent renal vascular relaxation and a reduced sensitivity to insulin are present in patients with essential hypertension. A link may be present between the abnormality of the L-arginine/nitric oxide/cyclic GMP pathway and insulin resistance in patients with essential hypertension.
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PMID:Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension. 903 15

1. Previous studies have indicated that younger hypertensive subjects may have abnormal endothelium-dependent relaxation, which could contribute to the elevated peripheral resistance seen in established hypertension. This study was designed to examine the functional behaviour of the endothelium of small arteries from elderly hypertensive and normotensive subjects. 2. Resistance arteries were obtained from gluteal biopsies taken under local anaesthesia in 28 subjects of mean age 70 (range 60-76) years, and studied in an isometric myograph. Eighteen subjects had untreated essential hypertension, and 10 were normotensive. 3. After measurement of the contractile response to noradrenaline, relaxation responses to a variety of endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (iloprost and sodium nitroprusside) mechanisms were assessed in vessels precontracted with noradrenaline. Endothelium-dependent responses were also studied after incubation with NG-nitro-L-arginine to inhibit nitric oxide synthase. 4. There were no significant differences in the contraction or relaxation responses between elderly subjects with or without high blood pressure. Inhibition of nitric oxide synthase prevented any relaxation with acetylcholine and significantly attenuated the relaxation with bradykinin. Near-complete relaxation was however achieved with the endothelium-independent vasodilator sodium nitroprusside. 5. Hypertension in elderly subjects is not associated with a reduction in endothelial vasodilating function in the subcutaneous vessels of the gluteal region compared with age-matched normotensive controls. The results of this study do not support the hypothesis of a defect of resistance artery endothelium-dependent relaxation in the pathophysiology of hypertension in the elderly.
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PMID:Endothelial function in subcutaneous resistance arteries from elderly hypertensive and normotensive subjects. 905 14

The prevalence of plasma platelet-activating factor (PAF) acetylhydrolase deficiency was investigated in 477 healthy Japanese individuals and 985 patients with various cardiovascular diseases. The genotype for this enzyme with regard to a G994-->T mutation (MM, normal; Mm, heterozygote; mm, mutant homozygote) was determined by an allele-specific polymerase chain reaction in 80 subjects shown to have no or low plasma activity (<10 nmol/min/ml). In 72 subjects, the genotype was consistent with plasma enzyme activity; 44 individuals with no activity were mm, and 28 with low activity were Mm. However, eight subjects with the MM genotype showed plasma enzyme activities of <10 nmol/min/ml. Determination of the DNA sequence of exon 9 of the plasma PAF acetylhydrolase gene in these eight subjects revealed a previously unidentified A1001-->G missense mutation, resulting in a Gln281-->Arg substitution, in a 72-year-old woman with coronary artery disease, essential hypertension, and no plasma enzyme activity. Site-directed mutagenesis in vitro showed that the corresponding recombinant mutant protein lacked PAF acetylhydrolase activity. Thus, the Gln281-->Arg substitution appears responsible for the loss of plasma PAF acetylhydrolase activity.
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PMID:Loss of activity of plasma platelet-activating factor acetylhydrolase due to a novel Gln281-->Arg mutation. 924 31

Endothelial dysfunction may be related to cardiovascular risk factors, such as aging, hypertension, and atherosclerosis. We investigated whether aging and hypertension independently alter endothelial function in the renal circulation in humans in the absence of abnormalities in lipid and glucose metabolism. L-Arginine (500 mg/kg over 30 minutes) was intravenously administered to 33 patients with essential hypertension and 35 normotensive subjects. The L-arginine-induced increases in renal plasma flow (10.1+/-0.8% versus 15.8+/-0.9%, P<.05) and plasma cGMP (53+/-4% versus 82+/-5%, P<.05) were significantly smaller in patients with essential hypertension than in the normotensive subjects. Multivariate stepwise regression analysis showed that age (P<.0002) and the mean blood pressure (P<.0001) were independently and negatively correlated with the renal plasma flow response to L-arginine. Age (P<.002), mean blood pressure (P<.0001), and male sex (P<.05) were independently correlated with the L-arginine-induced increase in plasma cGMP. The peak change in plasma cGMP was significantly correlated with the L-arginine-induced increase in renal plasma flow (r=.63, P<.001). These findings suggest that aging and hypertension may independently impair endothelium-dependent renovascular dilation and that this effect may be caused at least in part by a decrease in nitric oxide production.
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PMID:Aging and severity of hypertension attenuate endothelium-dependent renal vascular relaxation in humans. 926 Sep 89

The activity of NO-synthase and formation of NO (EDRF) were assessed by an increase in the activity of NO-dependent hyanilate cyclase in response to L-arginine in vitro in platelets of 61 pregnant females (39, 8 14 with essential hypertension, preeclampsia and healthy controls, respectively) and in 9 hypertensive nonpregnant females. Compared to healthy pregnant females, EDRF synthesis activity was inhibited in hypertensive gravidas but enhanced in preeclampsia patients. Effectiveness of exogenic donator NO (transdermal nitroglycerine, Nitroderm NNS 5) was studied in a randomised trial of 76 gravidas with essential hypertension (EH), EH and chronic glomerulonephritis (GN). 39 of them were given transdermal nitroglycerine, 37 received acetylsalicilic acid and curantil. The number of treatment failures was the same in both groups. The conclusion is made that nitro compounds are adequate for use in EH and chronic GN gravidas.
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PMID:[Nitric oxide: its role in the development of pregnancy complications and in their prevention in women with hypertension and chronic glomerulonephritis]. 929 65


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