Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the role of nitric oxide (NO) in the inherited resistance or susceptibility to hypertension in the Sabra hypertension-prone (SBH) and hypertension-resistant (SBN) rat. Basal mean arterial blood pressure was significantly greater in SBH than in SBN rats. Phenylephrine elevated blood pressure to a similar extent in both substrains, whereas the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) had a greater pressor effect in SBN rats. The vasoconstrictor potency of phenylephrine was significantly higher in endothelium-intact aortic rings from the SBH rat, whereas the vasoconstrictor potency of L-NMMA was higher in those from the SBN substrain. Acetylcholine-induced endothelium-dependent relaxation was greater in aortic rings from SBN rats. The vasodilator potency of glyceryl trinitrate was significantly higher in aortic rings from SBH rats and was enhanced after endothelium removal. Both the activity of calcium-dependent NO synthase from aortic endothelial cells and the basal concentration of nitrite/nitrate in plasma were significantly greater in SBN than in SBH rats. In normotensive Wistar rats, basal mean arterial blood pressure, the pressor effect of L-NMMA, endothelial NO synthase activity, and plasma nitrite/ nitrate concentrations were all between the values in SBH and SBN rats. These results indicate that a decrease in NO generation plays a role in the susceptibility of SBH rats to hypertension. Furthermore, the resistance to hypertension in the SBN strain may be related to increased NO generation.
Hypertension 1996 Sep
PMID:Nitric oxide and the regulation of blood pressure in the hypertension-prone and hypertension-resistant Sabra rat. 879 18

The introduction of cyclosporin A (CsA) is considered a cornerstone advance in immunosuppression. However, serious side effects such as hypertension have fostered an important body of research regarding their pathophysiology. Although the participation of several vasoactive factors in the hypertensive response has been described, recent attention has focused on endothelium-derived vasoactive factors, and several reports describe an overproduction of endothelin-1 and a deficient endothelium-dependent vasodilation. In the case of the latter, no definitive clues for the precise molecular mechanisms have been provided. We demonstrate that endothelial cells in culture synthesize more NO in the presence of CsA for 24 h in a concentration-response manner. This augmentation is correlated with a threefold increase in the endothelial constitutive NO synthase (ecNOS) transcript, which is time dependent and maximal at 24 h. The CsA-induced increase in ecNOS mRNA expression was blocked by actinomycin D but unaltered by cycloheximide. Levels of ecNOS protein were also enhanced by CsA after 24 h. These data establish that NO synthesis is moderately enhanced in endothelial cells exposed to CsA for long periods of time and describe a new mode of regulating ecNOS gene expression.
...
PMID:Regulation of endothelial NO synthase expression by cyclosporin A in bovine aortic endothelial cells. 885 43

Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease then production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.
...
PMID:Chronic inhibition of nitric oxide synthase in Heymann nephritis. 888 33

1. Endothelial cells release nitric oxide (NO) and the putative endothelium-derived hyperpolarizing factor (EDHF) in response to an increase in shear stress and receptor stimulation. 2. Tests of endothelial function have principally used acetylcholine (ACh)-mediated relaxation of precontracted isolated blood vessels or increases in forearm blood flow measured by venous occlusion plethysmography. Basal NO release is tested by a rise in resistance during infusion of the NO synthase inhibitor L-NMMA. Potential traps for investigators looking to evoke endothelial dysfunction following reduced ACh responses are discussed. 3. Endothelial dysfunction appears to occur in large but not small arteries in human and animal hypertension. Patients with long-standing congestive heart failure have endothelial dysfunction in buttock skin resistance arteries and there is coronary artery endothelial dysfunction following coronary ischaemia. 4. Remodelled arteries from neointimal thickening as a result of coronary collateral development in dog heart and new angiogenic vessel growth following large artery occlusion in the rabbit hindlimb appear to have normal endothelial function in relation to NO release. 5. Development of specific NO synthase inhibitors, antagonists of EDHF and the constrictor peptide endothelin, will clarify the role of these endothelium-derived factors in the cause or maintenance of vascular dysfunction. Defining redundancy and hierarchy of importance of these vascular factors are areas for future resolution.
...
PMID:Role of the endothelium in the genesis of cardiovascular disease. 888 8

The vascular effects of endothelin-1 (ET-1) and the release of prostacyclin and nitric oxide (NO) evoked by this peptide were analyzed in anesthetized, mechanically ventilated pigs. ET-1 induced biphasic responses in both the pulmonary and systemic vascular beds characterized by a transient hypotension followed by a long-lasting hypertension. To evaluate the involvement of prostacyclin and NO in the ET-1-dependent vascular response, we used indomethacin to block cyclooxygenase and NG-nitro-L-arginine methyl ester (L-NAME) to block NO synthase. The results show that the systemic hypotensive response to ET-1 is mediated by the release of prostanoids and NO, but these are not responsible for the pulmonary hypotension. Indomethacin reduced the hypertensive effect of ET-1, showing that this peptide can also activate release of vasoconstrictor cyclooxygenase metabolites. When L-NAME was administered after indomethacin, the pulmonary vasoconstrictor activity of ET-1 was counterbalanced by NO. By contrast, in pigs pretreated with indomethacin plus L-NAME ET-1 caused transient systemic vasoconstriction, followed by progressive reduction of vascular tone, probably because of release of vasodilator agents other than prostanoids or NO.
...
PMID:Differential release of prostacyclin and nitric oxide evoked from pulmonary and systemic vascular beds of the pig by endothelin-1. 895 97

We examined the effects of chronic nitric oxide (NO) blockade on bone mineral status in growing rats. Oral administration of NG-nitro-L-arginine methyl ester (L-NAME) for 4 wk caused hypertension and a significant reduction in urinary NO2- and NO3- excretion. Four-week oral aminoguanidine (AG, 400 mg/dl of drinking water) did not alter blood pressure but caused a significant decrease in urinary NO2- and NO3-. Rats treated with L-NAME at doses of 20 and 50 mg/dl had normal bone mineral mass in the lumbar spine, but the highest dose (80 mg/dl) caused a slight decrease in bone mass. Chronic AG induced a significant spine osteopenia. This effect of AG was abolished by the simultaneous administration of L-arginine (2.0 g/dl). AG-induced osteopenia was associated with a significant increase in urine excretion of collagen cross-links with normal serum osteocalcin. These findings indicate that chronic AG administration can cause an imbalance between bone resorption and formation, resulting in a decrease in bone mass in growing rats, and suggest that NO produced by inducible NO synthase plays an important role in basal osteoclast bone degradation activity in vivo.
...
PMID:Effect of nitric oxide synthase inhibitors on bone metabolism in growing rats. 896 73

The medullary portion of the kidney plays a crucial role in the control of sodium and water excretion and arterial pressure. This control is anomalous in hypertension and may be related to an impaired renal nitric oxide (NO) production. We have measured the activity of NO synthase (NOS) in the renal medulla, renal cortex, heart, and aorta from normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Enzyme activity was determined by measuring the conversion of 14C-L-arginine to 14C-L-citrulline. Ca2+-dependent NOS activity was considerably higher in the renal medulla than in the other tissues studied, both in WKY and SHR. The medulla and heart of the SHR displayed a higher Ca2+-dependent NOS activity compared to that of WKY. No differences were found in the Ca2+-independent NOS activity, except for the renal cortex of the SHR, which was higher than in the rest of the tissues. These observations indicate that the renal medulla has a high relative capacity to synthesize NO and suggest that the impaired renal medullary control of arterial pressure of genetic hypertension is not due to a reduced NO production by the kidney.
...
PMID:Nitric oxide synthase activity in renal cortex and medulla of normotensive and spontaneously hypertensive rats. 897 97

Nitric oxide (NO) is produced by three isoforms of NO synthase which catalyze the oxidation of L-arginine. Endothelial and neuronal NO synthases are constitutive and activated by an increase of intracellular calcium concentration. Activity of the inducible NO synthase is implied in inflammatory processes and does not depend on intracellular calcium. In the vessels, NO induces an active vasodilatory tone. Inhibition of NO synthases by L-arginine analogs results in a long-lasting pressor effect with renal damage, which demonstrates the role of the NO in the control of blood pressure and renal function. A defect of NO synthesis by endothelial or renal cells could be involved in the pathogenesis of salt-sensitive hypertension whereas, in other forms of hypertension, vascular NO would have a compensatory role. In the kidney, NO regulates glomerular filtration by vasodilating the glomerular afferent and, to a lesser extent, efferent arterioles and by increasing the ultrafiltration coefficient (Kf). NO is implied in the relationship between renal perfusion pressure and natriuresis and alters the tubulo-glomerular retrocontrol. The effects of the glomerular induction of NO synthase are under evaluation in various models of glomerulonephritis.
...
PMID:[Role of nitric oxide in the regulation of arterial pressure and renal function]. 899 Oct 28

We investigated the influence of endothelial nitric oxide (NO) on the pulmonary pressor activity of the stable thromboxane A2 analogue, U-46619 (9,11-dideoxy-9 alpha-(methanoepoxy) prostaglandin F2 alpha), in anesthetized open-chest Sprague-Dawley rats (n = 6-9 per group). NO synthase inhibition, as obtained by N omega-nitro-L-arginine methyl ester (L-NAME; 0.63 mg/kg i.v. + 20 mg/kg/h), induced sustained systemic hypertension (mean maximal increase, delta, in mean systemic arterial pressure = 38 +/- 6 mmHg; P < 0.05 vs. vehicle) associated with slight bradycardia (delta heart rate = -42 +/- 8 beats/min; P < 0.05 vs. vehicle) and delayed- (> 30 min) onset pulmonary hypertension (delta mean pulmonary arterial pressure = 10 +/- 3.4 mmHg; P < 0.05 vs. vehicle). In separate experiments, when mean systemic arterial pressure was maximally increased by L-NAME, the difference between mean pulmonary arterial pressure and mean left atrial pressure was greater in L-NAME-treated rats (41 +/- 16% compared to 10 +/- 1% in the vehicle group; P < 0.05), strongly suggesting that spontaneously released NO modulated pulmonary vascular resistance. L-Arginine at a dose which reduced by approximately 50% the L-NAME-associated systemic hypertension did not alter the late rise in mean pulmonary arterial pressure (delta mean pulmonary arterial pressure = 12 +/- 4 mmHg; P = NS vs. L-NAME alone). U-46619, elicited rapid, dose-dependent, and transient increases in mean pulmonary arterial pressure (delta = 8.8 +/- 2.0 and 21.2 +/- 1.9 mmHg at 1.25 and 20 micrograms/kg i.v. respectively; both P < 0.01 vs. vehicle). U-46619 (1.25 micrograms/kg)-induced increases in mean pulmonary arterial pressure were fully antagonized by the thromboxane A2/prostanoid (TP) receptor antagonist, SQ 29,548 ([1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]]-7-[3-[[2-[(phenyl-amino)-carbonyl] hydrazino] methyl]-7-oxabicyclo [2.2.1]hept-2-yl]-5-heptenoic acid) (0.63 mg/kg i.v. + 0.63 mg/kg/h). Injection of U-46619 (1.25 micrograms/kg), 15 min after L-NAME administration, evoked a 24.7 +/- 0.9 mmHg increase in mean pulmonary arterial pressure (P < 0.01 vs. U-46619 in control rats), which was (i) greater than that produced by a 16-fold higher dose of U-46619 alone, (ii) fully antagonized by SQ 29,548, (iii) significantly attenuated during coadministration of L-NAME and L-arginine (10 mg/kg i.v. + 160 mg/kg/h; delta mean pulmonary arterial pressure = 14.6 +/- 4.3 mmHg; P < 0.05 vs. U-46619 following L-NAME alone and P = NS vs. U-46619 in control rats). These results indicate that, under normal circumstances, pulmonary vasomotor tone is regulated by spontaneously released NO. Moreover, pulmonary vascular NO attenuates TP receptor-mediated pressor responses, strongly suggesting that in addition to mediating pulmonary vasoconstriction, TP receptor activation also concomitantly releases NO within the pulmonary vasculature.
...
PMID:Nitric oxide regulation of TP receptor-mediated pulmonary vasoconstriction in the anesthetized, open-chest rat. 899 19

The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: NG-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20-80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-beta-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-beta-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.
...
PMID:Renal functional measurements in young rats with chronic inhibition of nitric oxide synthase. 900 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---