Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was aimed at investigating whether the regulation of vascular renin-angiotensin and endothelin (ET) systems is altered by a chronic blockade of nitric oxide (NO) synthesis. Male Sprague-Dawley rats were supplemented with N(G)-nitro-L-arginine methyl ester (L-NAME, 100mgl(-1)) in drinking water for 4 weeks to inhibit the endogenous synthesis of NO. The mRNA expressions of renin, angiotensin converting enzyme (ACE), type-1 angiotensin II receptor (AT1R), ET-1, type-A ET receptor (ET(A)), and neutral endopeptidase (NEP) were determined in the thoracic aorta by reverse transcription-polymerase chain reaction. The treatment with L-NAME significantly increased the blood pressure, while it decreased the tissue levels of nitrite/nitrate. The mRNA expression of renin, ACE, and AT1R was increased in the aorta. The protein expression of AT1R assessed by Western blot analysis was also increased. The expression of ET-1 and ET(A) mRNA was increased, whereas that of NEP mRNA decreased. The increased expression of renin-angiotensin and ET system genes and the decreased expression of NEP may in part be causally related with the development of hypertension induced by a chronic blockade of NO synthesis.
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PMID:Upregulation of vascular renin-angiotensin and endothelin systems in rats inhibited of nitric oxide synthesis. 1241 41

Chronic liver diseases are accompanied by changes in splanchnic and systemic circulation. These changes are characterised by a reduction in peripheral vascular resistance and an increased cardiac output at rest. An increased release of nitric oxide (NO) has been proposed to play a role in the pathogenesis of vasodilatation and vascular hypocontractility. This study was designed to determine the nitric oxide metabolism measured as circulating nitrate levels in serum/urine in patients with chronic liver disease and cirrhosis. The nitrate concentrations were significantly increased in advanced degrees in cirrhosis Child B and C, and normal or even reduced in patients with chronic active hepatitis and early cirrhosis. In our study the connections between the extent of portal hypertension and nitrate levels were evident. The presence of ascites as well as the the progression of oesophageal varices were associated with higher circulating nitrate levels. The connection between increased nitric oxide production and the haemodynamic sequelae of portal hypertension is also apparent in the significant correlation between plasma renin and serum nitrate levels. Circulating nitrate levels also correlated to the serum interleukin-6 levels. This study demonstrated that the increased nitric oxide metabolism is associated with the haemodynamic alterations induced by portal hypertension.
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PMID:Elevated nitric oxide levels in patients with chronic liver disease and cirrhosis correlate with disease stage and parameters of hyperdynamic circulation. 1243 67

This study was designed to test the hypothesis that increased pressure itself could cause endothelial dysfunction and lead to decreased nitric oxide (NO) release, partly through effects on the tissue renin angiotensin system in hypertension. Cultured endothelial cells (ECs) isolated from the aortas of WKY rats were continuously exposed to a pressure of 150 mmHg in a CO2 incubator for 72 h using a pressure system, and the NOx (NO2 and NO3) and angiotensin II (Ang II) concentrations in the supernatant were measured. An Ang II type 1 receptor (AT1R) antagonist (losartan) and an Ang II type 2 receptor (AT2R) antagonist (PD123319) were added to the medium. The expression of AT1R and AT2R mRNAs was also examined. Pressure loading significantly decreased the NO release from ECs. Concomitant administration of losartan restored NO release to the level before the application of pressure (p<0.001). This effect of losartan was blocked by simultaneous administration of PD123319, bradykinin type 2 receptor antagonist, and NO synthase inhibitor (p<0.05). The Ang II concentration was increased by pressure and was further increased by losartan. The gene expression of AT1R was not changed by pressure, but AT2R mRNA was increased almost 2-fold. These results indicate that high pressure itself attenuates NO release from ECs, and that losartan improves NO release by activating the bradykinin system via AT2R stimulation. In addition, the increase of AT2R gene expression in ECs during exposure to pressure may compensate for the reduction of NO.
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PMID:Contrasting effects of angiotensin type 1 and 2 receptors on nitric oxide release under pressure. 1245 33

Rats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to present differences in stimuli responses involving the renin-angiotensin system and in cardiovascular responses to an acoustic startle stimulus. Here we compared the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred rat strains. Blood pressure (BP) and heart rate (HR) were recorded in conscious rats, before and after a neurohumoral blockade obtained by successive administration of chlorisondamine, enalapril, a V1-vasopressinergic receptor antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280 ng/kg were injected randomly. Average dose-response curves were established. After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3 mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 microg/mL and 800 microL/min, i.v.) were used to reflect arterial wall structure. The maximal systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were higher in F344 compared with WKY (+86 +/- 3 mmHg vs. +71 +/- 3 mmHg, P < 0.01 for SBP, +31 +/- 2 mmHg vs. +18 +/- 1 mmHg, P < 0.001 for PP). After the ANG II type 1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344 and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP level following hydralazine was higher in F344 (F344: 48 +/- 2 mmHg vs. WKY: 37 +/- 3 mmHg, P < 0.01). The amplification in F344 of the vasoconstrictive response to ANG II mediated by AT1 receptors is compatible with a high number of AT1 receptors in this strain. In F344, the exaggerated systolic and PP responses to ANG II and the higher MBP level after hydralazine most likely reflect a structural modification of the arterial wall such as hypertrophic remodelling in F344.
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PMID:Different vascular responsiveness to angiotensin II in two normotensive rat strains. 1280 70

Two types of hypertensin have been demonstrated by means of counter-current distribution. The first type is the product of the action of the enzyme, renin, upon its substrate and has been designated hypertensin I. It can be rapidly converted to a second approximately equally pressor compound, hypertensin II, apparently through the action of an enzyme in the plasma which requires halide or nitrate for activation. A highly purified preparation containing horse hypertensins I and II caused an elevation of blood pressure when injected into human beings.
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PMID:The existence of two forms of hypertensin. 1313 Jul 99

The present study evaluates the participation of oxidative stress, tissue angiotensin II (Ang II) and endothelin (ET) in the effects of losartan on blood pressure (BP), ventricular hypertrophy and renal injury in spontaneously hypertensive rats (SHRs), and explores how these effects are modified when spontaneous hypertension is transformed in a low-renin model by the administration of deoxycorticosterone acetate (DOCA). The following groups were used: SHR-control, SHR+DOCA, SHR+losartan and SHR+DOCA+losartan. Tail systolic BP was measured once a week. After 9 weeks of treatment, direct BP and metabolic, morphological, biochemical and renal variables were measured. DOCA administration to SHRs produced an increase in BP, ventricular hypertrophy, renal weight, proteinuria, renal histopathological lesions, urinary excretion of isoprostane F2alpha and ET levels in the renal cortex. Losartan reduced BP, plasma malondialdehyde levels, urinary excretion of isoprostane F2alpha, renal Ang II and renal and urinary levels of ET in the SHR and DOCA-treated SHR groups. Losartan increased plasma nitrite/nitrate in SHRs, but not in low-renin DOCA-treated SHRs. Losartan reduced ventricular hypertrophy and ventricular Ang II in SHRs, but not in DOCA-treated SHRs. Losartan significantly decreased proteinuria and renal injury in DOCA-treated SHRs. We conclude that (i) the DOCA-induced aggravation of hypertension, ventricular hypertrophy and renal injury in SHRs is accompanied by augmented oxidative stress and increased levels of ET in the renal cortex, which could contribute to their development; and (ii) losartan reduced oxidative stress and renal Ang II and ET in SHRs and DOCA-treated SHRs, which might contribute to its antihypertensive and renoprotective effects, regardless of renin status.
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PMID:Protective effects of the angiotensin II type 1 (AT1) receptor blockade in low-renin deoxycorticosterone acetate (DOCA)-treated spontaneously hypertensive rats. 1452 6

Since hepatorenal syndrome is a functional renal failure due to renal ischemia in cirrhotics with refractory ascites, we investigated whether increased intra-abdominal pressure (IAP) impairs the renal function and perfusion in cirrhotic portal hypertensive rats. Eight groups of 32 rats each were studied, including 4 control and 4 CCl(4) cirrhotic groups. These were subdivided into two groups each, with and without an increased IAP, and further subdivided into groups of rats with and without NO inhibition. IAP was increased to 20 mm Hg for 7 consecutive days by means of an intraperitoneally placed balloon filled with water. The animals were studied in normal conditions and after inhibition of NO synthesis. Changes in mean arterial pressure and renal microcirculation by means of femoral artery catheterization and laser-Doppler technique, respectively, were recorded. Venous samples for determination of plasma renin-aldosterone activity, biochemical parameters of liver and renal function, and plasma nitrite/nitrate levels as an index of NO synthesis were drawn. Cirrhotic rats showed decreased renal microcirculation (P = 0.05), while elevated IAP produced a further decrease (P = 0.01). Renin-aldosterone levels found increased (P = 0.001) in cirrhotics, and elevated IAP produced a further increase (P = 0.01] in both groups. Inhibition of NO synthesis resulted in a nonsignificant decrease in both renal microcirculation and renin-aldosterone levels in all experimental groups. Liver and renal function was found to be impaired in cirrhotics, but increased IAP had a nonsignificant further functional impairment in both organs. In conclusion, chronically elevated IAP in cirrhotic rats is associated with an increase in renin-aldosterone levels and significant impairment of renal perfusion.
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PMID:The influence of continuous seven-day elevated intra-abdominal pressure in the renal perfusion in cirrhotic rats. 1457 84

Angiotensin-converting enzyme (ACE) inhibitors effectively interfere with the renin-angiotensin system and exert various beneficial actions on vascular structure and function beyond their blood pressure-lowering effects. Data from experimental studies showed that angiotensin-converting enzyme inhibitors can attenuate the development of atherosclerosis in a wide range of species. The postulated mechanisms of this atheroprotective effect are the antioxidant actions of angiotensin-converting enzyme inhibitors and their enhancement of the endothelial elaboration of bioactive nitric oxide. The aim of this study was to assess the comparative effects of three angiotensin-converting enzyme inhibitors on endothelial nitric oxide production and action, and on endothelial oxidative stress. Using bovine aortic endothelial cells in culture grown to confluence, we examined the effects of 1, 10, 30 and 60 microM of each of captopril, zofenopril and enalapril on nitrite/nitrate accumulation in the media, cyclic GMP accumulation in the cell lysate, and F(2)-isoprostanes in lipid extracts from the cells. Results showed that the sulfhydryl angiotensin-converting enzyme inhibitor zofenopril has unique properties compared with captopril and enalapril. This compound improves nitric oxide production and bioactivity, and does so in conjunction with decreased endothelial cell oxidant stress. The biochemical basis for this protective mechanism is not entirely clear; however, these actions suggest that zofenopril may reduce endothelial effects of risk factors for atherothrombotic disease.
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PMID:The effect of angiotensin-converting enzyme inhibition on endothelial function and oxidant stress. 1466 9

Confinement and inactivity induce considerable psychological and physiological modifications through social and sensory deprivation. The aim of the SFINCSS-99 experiment was to determine the cardiovascular and hormonal pattern of blood volume regulation during long-term isolation and confinement. Simulation experiments were performed in pressurized chambers similar in size to the volumes of modern space vehicles. Group I consisted of four Russian male volunteers, who spent 240 days in a 100-m(3 )chamber. Group II included four males (one German and three Russians) who spent 110 days in isolation (200-m(3) module). The blood samples, taken before, during and after the isolation period, were used to determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and osmolality levels. From the urine samples, electrolytes, osmolality, nitrites, nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and metanephrine levels were determined. The increase in plasma volume (PV) that is associated with a tendency for a decrease in plasma active renin is likely to be due to decreased sympathetic activity, and concords with the changes in urinary catecholamine levels during confinement. Urinary catecholamine levels were significantly higher during the recovery period than during confinement. This suggests that the sympathoadrenal system was activated, and concords with the increase in heart rate. Vascular resistance is determined by not only the vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in urine, as an indicator of nitric oxide release, did not reveal any significant changes. Analysis of data suggests that the duration of the isolation was a main factor involved in the regulation of hormones.
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PMID:Hormonal changes during long-term isolation. 1472 79

Accumulating evidence shows that inhibition of the vascular renin-angiotensin system results in suppression of injury-elicited neointima formation. We attempted to determine whether or not combined treatment with an angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) has an additive inhibitory effect on balloon-injury-elicited neointima formation in the carotid artery. Male Sprague-Dawley rats were treated with an ARB (valsartan: 3 mg/kg/day) and/or an ACEI (benazepril: 0.3 mg/kg/day) from 1 week before until 2 weeks after balloon injury. Experiments were also conducted with one-third of the dose combination used in the original experiments. Both ARB and ACEI inhibited neointima formation without any blood pressure changes. The full-dose combination lowered blood pressure and suppressed neointima formation significantly compared with the levels in the groups treated with either ACEI or ARB alone. The low-dose combination without blood pressure reduction also inhibited neointima formation to a similar extent as the full-dose combination. We measured 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, and nitrite and nitrate (NOx), an index of nitric monoxide production, in media conditioned by the injured artery. NOx production was lower and 8-iso-PGF2alpha was higher in the media of the injured artery, compared with those in the normal artery. ACEI restored NOx production more dramatically than ARB, and ARB suppressed 8-iso-PGF2alpha markedly compared with ACEI. These results suggest that the combination of an ARB and an ACEI exerts an additive inhibitory effect, presumably through an increase in production and bioavailability of NO from the endothelium.
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PMID:Combined treatment with an AT1 receptor blocker and angiotensin converting enzyme inhibitor has an additive effect on inhibiting neointima formation via improvement of nitric oxide production and suppression of oxidative stress. 1500 76


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