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

Little is known about the effect of chronic angiotensin-converting enzyme inhibition on the catecholamine levels in fowls. In this study, we investigated the effects of chronic lisinopril dihydrate (Ld) application on the plasma levels of adrenaline and noradrenaline and on the blood pressure. Lisinopril was given in different concentrations (25, 75 and 250 mg/l drinking water) to the white Leghorn chickens for 9 weeks, while the control group drank tap water only. Twenty-eight hours after the last lisinopril application, arterial blood pressure (BP), plasma adrenaline and noradrenaline levels, plasma renin (PRA) and plasma angiotensin-converting enzyme (ACE) activities were determined. In all concentrations, lisinopril significantly increased PRA and decreased ACE activities. Arterial BP was decreased only in the group receiving high lisinopril concentration (Controls 119+/-10.27, Ld3 98+/-5.4 mm Hg). However, the lower lisinopril concentrations did not alter arterial BP compared to the control group. Plasma noradrenaline levels were decreased in a concentration-dependent manner (47-58%), but plasma adrenaline levels remained unchanged. The heart weight/body weight ratio was not changed in any of the lisinopril-treated groups. The persistent decrease in the blood pressure after lisinopril treatment was not directly related to a decrease of plasma ACE activity or plasma noradrenaline levels. Its mechanism still remains to be elucidated.
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PMID:Long-term lisinopril dihydrate application decreases plasma noradrenaline but not adrenaline levels in chickens. 1080 21

We examined the role of the central nervous system, and particularly the renin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L-arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA(A) agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model.
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PMID:Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats. 1121 29

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits not only hematopoietic cell proliferation but also fibroblast proliferation and collagen synthesis in vitro. Ac-SDKP also prevents collagen deposition and cell proliferation in the left ventricle (LV) in rats with renovascular hypertension (renin dependent). However, it is not clear whether Ac-SDKP has similar effects in a model of renin-independent hypertension (aldosterone-salt). Using a hypertensive rat model of cardiac and renal fibrosis created by chronic elevation of circulating aldosterone (ALDO) levels, we examined the effect of Ac-SDKP on blood pressure, cardiac and renal fibrosis and hypertrophy, and proliferating cell nuclear antigen (PCNA) expression in the LV and left kidney. Uninephrectomized rats were divided into 4 groups: (1) controls that received tap water, (2) rats that received ALDO (0.75 microgram/h SC) and 1% NaCl/0.2% KCl in drinking water (ALDO-salt), (3) rats that received ALDO-salt plus Ac-SDKP 400 microgram. kg(-1). day(-1) SC, and (4) rats that received ALDO-salt plus Ac-SDKP 800 microgram. kg(-1). d(-1) SC. After 6 weeks of treatment, the ALDO-salt group was found to have significantly increased blood pressure with decreased body weight and plasma renin concentration (P<0.05), LV and renal hypertrophy as well as renal injury, significantly increased collagen content in both ventricles and kidney as well as increased collagen volume fraction in the LV (P<0.0001), and significantly increased interstitial and perivascular PCNA-positive cells in the LV and kidney (P<0.0001). Ac-SDKP at 800 microgram. kg(-1). d(-1) markedly prevented cardiac and renal fibrosis (P<0.005) without affecting blood pressure or organ hypertrophy. It also suppressed PCNA expression in the LV and kidney in a dose-dependent manner. We concluded that Ac-SDKP prevents increased collagen deposition and cell proliferation in the heart and kidney in ALDO-salt hypertensive rats. Because ACE inhibitors increase plasma and tissue Ac-SDKP and decrease cardiac and renal fibrosis, we speculate that Ac-SDKP may participate in the antifibrotic effect of ACE inhibitors.
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PMID:Antifibrotic effects of N-acetyl-seryl-aspartyl-Lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. 1123 Mar 75

In Western society, the triad of hypertension, metabolic syndrome and obesity (which caries a high risk for renal disease) is increasing, as is the intake of caffeine. However, no information is available regarding the metabolic or renal consequences of caffeine consumption in this complex disease entity. The purpose of this study was to investigate the effects of chronic caffeine consumption on renal function and metabolic status in obese ZSF1 rats, an animal model of obesity, hypertension and the metabolic syndrome. Fifteen, 18-week-old male, obese ZSF1 rats were randomized to drink tap water (Cont, n = 8) or 0.1% solution of caffeine (Caff, n = 7) for 8 weeks. Metabolic and renal function measurements were performed at baseline and after 4 and 8 weeks of treatment. Caffeine treatment significantly (p < 0.05) reduced body weight, food, and fluid consumption and improved insulin sensitivity (fasting insulin 129.6+/-8.1 vs 97.5+/-3.6 microIU/mL; fed insulin 146.3+/-8.5 vs 110.6+/-3.4 microIU/mL; fasting glucose 138.7+/-13.4 vs 145+/-8.0 mg/dL; fed glucose 373+/-19.4 vs 283.3+/-19.6 mg/dL, Cont vs Caff, respectively). After 8 weeks of caffeine treatment, animals were less glycosuric as compared with control group. Area under glucose curves (AUC-glucose) in oral glucose tolerance test did not differ between the two groups (AUC- glucose: 592.5+/-42.7 vs 589.5+/-20.5 mg/dL x h, Cont vs Caff), whereas caffeine treatment significantly decreased AUC of insulin (AUC-insulin: 257.77+/-12.9 vs 198.0+/-5.9 microIU/mL x h, Cont vs. Caff, p<0.05). No differences were found with regard to plasma triglycerides and glycerol levels; however, caffeine significantly increased cholesterol levels after 4 and 8 weeks (2F-Anova, p<0.001). Moreover, caffeine significantly decreased creatinine clearance after 4 and 8 weeks (CrCl, Cont: 3.5+/-0.4, Caff: 2.2+/-0.2 L/kg/day, p<0.05) and increased protein/CrCl ratio (Cont: 323+/-30, Caff: 527+/-33 mg/L/day). Caffeine treatment for 8 weeks tended to increase plasma norepinephrine levels (p<0.06), but the two groups did not differ with regard to plasma renin activity, blood pressure, renal blood flow or and renal vascular resistance. The study indicates that caffeine improves insulin sensitivity but increases plasma cholesterol levels and impairs renal function in obesity with the metabolic syndrome and hypertension. Our results imply that the health consequences of chronic caffeine consumption may depend heavily on underlying pathophysiology process.
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PMID:Renal and metabolic effects of caffeine in obese (fa/fa(cp)), diabetic, hypertensive ZSF1 rats. 1141 48

Previously, we had found that inhibition of the renin-angiotensin system in the early lifespan of spontaneously hypertensive rat could prevent the development of hypertension in this animal model. In the present study we evaluated the responses of blood pressure and renal function to intracerebroventricular administration of angiotensin II in long-term captopril-treated spontaneously hypertensive rats. Spontaneously hypertensive rats had been mated and their pups were treated with captopril through drinking water after birth. Age-matched Wistar-Kyoto and spontaneously hypertensive rats drinking tap water were used as control groups. At 4 months of age, the basal mean arterial blood pressure of captopril-treated hypertensive rats was the lowest among those of controlled hypertensive and normotensive rats (98+/-5 vs. 160+/-4 and 126+/-4 mmHg, respectively). Intravenous administration of angiotensin II caused similar increments of blood pressure in all rat groups. However, intracerebroventricular administration of angiotensin II to captopril-treated hypertensive rats induced a significantly less increase of arterial blood pressure in comparison with other groups. The sensitivity of baroreflex in captopril-treated hypertensive rats was also the lowest among all rat groups. The basal urine flow, sodium and potassium excretion rates, and osmolar clearance of captopril-treated hypertensive rats were significantly higher than those of controlled hypertensive rats. Intracerebroventricular infusion of angiotensin II caused significant increases in urine flow, electrolytes excretion, osmolar clearance, and free water reabsorption rate of both normotensive and controlled hypertensive rats. However, the same angiotensin II treatment did not change any of the renal excretion indices in captopril-treated hypertensive rats. Our results suggest that lifetime captopril treatment can decrease the activity of the renin-angiotensin system in the brain of hypertensive animals, which caused increases in basal urine flow and excretion of electrolytes and enhanced the sensitivity of baroreflex. It is likely that changes in the renal and baroreflex functions underlie the prevention of hypertension elicited by long-term captopril treatment.
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PMID:Blunted renal responses to angiotensin II infusion in lifetime captopril-treated spontaneously hypertensive rats. 1153 Sep 45

Renin-angiotensin-aldosterone system blockade has been shown to protect against renal damage in salt-supplemented, stroke-prone spontaneously hypertensive rats (SHRsp). Based on intermittent tail-cuff blood pressure (BP) measurements, it has been claimed that such protection is BP-independent and mediated by a blockade of the direct tissue-damaging effects of angiotensin and/or aldosterone. BP radiotelemetry was performed for 8 weeks in approximately 10-week-old male SHRsp who received a standard diet and either tap water (n=10) or 1% NaCl to drink. Saline-drinking SHRsp were either left untreated (n=12), received enalapril (50 mg/L) in drinking fluid (n=9), or had subcutaneous implantation of time-release 200-mg pellets of aldactone (n=10). The average systolic BP (mean+/-SEM) during the final 3 weeks was significantly higher (P<0.05) in untreated saline-drinking (215+/-6 mm Hg) SHRsp but not aldactone-treated (198+/-4 mm Hg) or enalapril-treated treated SHRsp (173+/-1 mm Hg), as compared with tap water-drinking SHRsp (197+/-3 mm Hg). Histological renal damage scores at 8 weeks paralleled the BP in all groups, with an excellent correlation (r=0.8, P<0.001, n=41). Moreover, a renal damage score of >5 was only observed in SHRsp whose average systolic BP during the final 3 weeks exceeded 200 mm Hg, indicating a threshold relation with BP. These data show that protection by renin-angiotensin-aldosterone system blockade in this model is BP-dependent and mediated by preventing the severe increases in BP seen in untreated salt-supplemented SHRsp and further underscore the limitations of interpretations based on conventional tail-cuff BP measurements.
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PMID:Renoprotection by ACE inhibition or aldosterone blockade is blood pressure-dependent. 1257 79

Acute treatment with the diuretic furosemide (Lasix) produces a reduction in plasma Na(+) and volume as well as increased thirst and salt appetite. The resulting hypovolemia stimulates the well-known counter-regulatory physiological response from the renin-angiotensin-aldosterone system. However, the neurochemical players underpinning the behavioral responses of thirst and salt appetite are less clear. Previously, we have reported that salt-replete deoxycorticosterone (DOCA) treatment activates mesolimbic structures associated with reward and goal-seeking behavior. The present study was designed to test whether the same brain regions are affected in a salt-depleted state. In experiment 1, two groups of adult male Sprague-Dawley (SD) rats were injected with Lasix (10 mg/rat, s.c.) and 18 h later were allowed access either to 2% NaCl solution ('Lasix+salt') or only to tap water ('Lasixnosalt') for 2 h. For comparison purposes, a third group received an isotonic saline injection instead of Lasix and was allowed access to the 2% salt solution (Vehicle). All groups were permitted 24 h access to tap water. We found no differences in dynorphin-mRNA levels in any striatal and accumbal regions among any of the treatment groups. However, as found previously in DOCA-treated rats, there were increased enkephalin (ENK)-mRNA and decreased dopamine transporter (DAT) binding levels throughout the striatum in Lasix+salt and decreased ENK-mRNA in Lasixnosalt rats versus Vehicle. In experiment 2, the involvement of the ENKergic and/or dopaminergic system was tested in rats divided into the same three groups described in experiment 1. However, before access to salt or water, the Lasix+salt and the vehicle groups were administered either a delta-opioid, naltrindole or a dopamine D(2) antagonist, raclopride. Only the naltrindole-treated rats showed a blunted intake of salt solution. Thus, these findings along with our neurochemical results suggest that mesolimbic enkephalin might impact salt intake through dopaminergic systems.
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PMID:Involvement of mesolimbic structures in short-term sodium depletion: in situ hybridization and ligand-binding analyses. 1284 26

We studied the effect of hypercholesterolemia on the pressure-sensing and regulating ability of the kidneys, using an acute hemorrhage model to provide 40% and 60% reduction in the blood pressure of hypercholesterolemic and control rats. The control group (n = 22) was fed a normal rat pellet diet and tap water; the experimental group (n = 22) received a diet containing 2% cholesterol/0.2% thaurocholate. Half the animals were subjected to 6 mL/kg bw and the others to 12 mL/kg bw of bleeding for 1 min. Blood pressure recording and proper samplings were done before bleeding and during the 20 min post-hemorrhagic period for analysis. Despite a finding of hypercholesterolemia in the experimental group, kidney cholesterol content as well as its function remained unchanged. Following an initial 40% decrease in rats bled 6 mL/kg bw, 20 min later the mean blood pressure returned to 90% of its initial value in control rats and to 70% of its basal level in hypercholesterolemic rats. A similar delay in pressure normalization occurred in rats subjected to 12 mL/kg of bleeding. Plasma renin activity remained unaffected. We conclude that dietary hypercholesterolemia delays the normalization of blood pressure after hemorrhage without affecting the sensing ability of kidneys, and that the kidneys are less sensitive than other organs to plasma cholesterol levels.
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PMID:The role of cholesterol on the pressure sensing ability of kidneys in rats. 1519 6

To clarify the physiological roles of the renin-angiotensin-aldosterone system (RAAS) and arginine vasotocin (AVT) on body fluid regulation in amphibians, we measured plasma concentrations of aldosterone (ALDO), angiotensin II (ANG II), and AVT after various osmotic challenges in the marine toad, Bufo marinus (Bufonidae). Hematocrit value (Ht) as an indicator of plasma volume, plasma osmolality and concentrations of plasma components (Na(+), Cl(-), K(+), and urea) were also measured. The toads were maintained under various osmotic treatments for 7 days. In dehydrated toads, plasma concentrations of ALDO, ANG II, AVT, and all plasma components measured were increased. In toads maintained in 300 mosmol/kg H(2)O NaCl solution, plasma osmolality, Na(+), Cl(-), urea, and plasma AVT concentrations were significantly increased, and Ht and plasma concentrations of ALDO and ANG II were significantly decreased. In toads maintained in tap water, plasma osmolality, and concentrations of Na(+) and ALDO were significantly decreased. We also estimated total body water (TBW), plasma volume (PV) using Evans Blue dye and Ht in the toads under various osmotic treatments. In dehydrated toads, TBW and PV were significantly decreased and Ht was significantly increased in comparison with those of control. In toads maintained in 300 mosmol/kg H(2)O NaCl solution, TBW and PV were significantly increased and Ht was significantly decreased in comparison with those of control. There was a significant negative correlation between Ht and PV or TBW. These results show that dehydration, which induces hypovolemic and hyperosmotic conditions, stimulates increases of plasma ALDO, ANG II, and AVT concentrations, while hypervolemic treatment induces decreases of plasma ALDO and ANG II concentrations. There were significant correlations between plasma osmolality and AVT concentration, between Ht and concentrations of RAAS hormones, and between plasma concentrations of ALDO and ANG II. These results suggest that volumetric and osmometric systems regulated by RAAS hormones and AVT are present in B. marinus.
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PMID:Plasma aldosterone, angiotensin II, and arginine vasotocin concentrations in the toad, Bufo marinus, following osmotic treatments. 1561 70

Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In the present study, we showed how serum and local angiotensin converting enzyme (ACE) alters during development of hypertension in chronic nitric oxide synthase blockade, a non-renin-dependent model of hypertension. Four experiments were performed in which animals were given N(omega)-nitro-L-arginine methyl ester (L-NAME) (50 mg kg(-1)) for 2, 4, 8 and 12 weeks. The control group rats received tap water. The ACE activity in serum, aorta, heart, kidney and lung was analyzed by high performance liquid chromatography (HPLC) and the structural change in aorta was investigated by measurement of cross-sectional area (CSA). Significant elevation of systolic blood pressure developed in chronically NO-blocked rats compared to controls. These results indicated that ACE activity in aortae and heart was gradually increased during development of hypertension and was more pronounced at higher blood pressure. Furthermore, there was a positive correlation between aortic cross-sectional area and elevation of blood pressure. These observations highlight the importance of the local ACE particularly in organs regulating hypertension (aorta and heart) during development of L-NAME-induced hypertension.
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PMID:Investigation of local ACE activity and structural alterations during development of L-NAME-induced hypertension. 1611 91


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