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

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to produce acute and chronic hypertension in many animal species, but the underlying mechanisms mediating the hypertension are not completely understood. In particular, the pathogenetic roles of sodium sensitivity and the sympathetic nervous system in this model of hypertension are controversial. The present study was designed to test the hypothesis that long-term administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to male Sprague-Dawley rats would produce a sodium-sensitive hypertension and that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. NG-Nitro-L-arginine methyl ester was added to drinking fluid for 8 weeks at a concentration of 16 mg/dL. Rats received tap water for the first 4 weeks of the study and were then divided into two groups and placed on either a normal or high sodium intake (ingestion of either tap water or 0.9% NaCl, respectively). Awake systolic blood pressure was measured by the tail-cuff method every week. Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long-term administration of L-NAME produced a marked and sustained elevation in arterial pressure without altering urine flow, or sodium excretion rate. NG-Nitro-L-arginine methyl ester-induced hypertension was accompanied by a decreased urinary excretion of the stable NO metabolites NO2- and NO3- and was aggravated when rats drank 0.9% NaCl in place of tap water. Urinary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME-treated rats increased significantly within the first week of the study compared with control rats. L-Arginine (2 g/dL in drinking fluid) completely reversed the elevation of arterial pressure as well as the decrease in urinary NO2- and NO3- excretion and the increased urinary excretion of catecholamines associated with L-NAME treatment by 3 weeks of concomitant administration. 4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve activity may, at least in part, contribute to the sodium sensitivity in this type of hypertension.
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PMID:Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats. 1069 24

Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO2/NO3). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 microg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO2/NO3 after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min. The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.
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PMID:Protective effects of imidapril on He-Ne laser-induced thrombosis in cerebral blood vessels of stroke-prone spontaneously hypertensive rats. 1082 69

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative stress. We examined the effect of chronic blockade of nitric oxide (NO) on urinary excretion of 8-OHdG in rats. Two types of NO synthase inhibitor were used: N(G)-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, 50 and 80 mg/dl of drinking water), but not AG (400 mg/dl), for 4 weeks induced systemic hypertension and a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME also showed a significant increase in urinary 8-OHdG excretion compared with the control animals. The effects of L-NAME (50 mg/dl) on blood pressure and urinary excretion of NO2/NO3- and 8-OHdG were restored by a large dose of L-arginine (2.0 g/dl). Chronic AG administration did not significantly alter urinary 8-OHdG excretion. On combining all the data, there was a significant negative correlation between urinary NO2-/NO,- and 8-OHdG. These observations suggest the importance of constitutive NO synthase activity in the maintenance of oxidant buffering capacity in rats. Oral administration of L-NAME may serve as a model of hypertension due to chronic NO deficiency with increased oxidative stress.
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PMID:Increased oxidative stress in rats with chronic nitric oxide depletion: measurement of urinary 8-hydroxy-2'-deoxyguanosine excretion. 1090 40

Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP-induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure.
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PMID:[The effect of exogenous nitric oxide on endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats]. 1119 97

Transgenic TGR(mREN2)27 (TGR) rats are an animal model of fulminant hypertension characterized by an inverse circadian blood pressure profile. The present study addressed the contribution of nitric oxide (NO) synthesis and baroreflex function to hypertension and the inverse blood pressure pattern. NO synthesis was measured at four different times of day indirectly by excretion of NO metabolites (NOx: NO2- and NO3-) in the urine of 5- and 11-week-old TGR and Sprague-Dawley (SPRD) controls. Blood pressure, heart rate, and motor activity were recorded in age-matched rats of both strains using an implantable telemetry system. Beat-to-beat recording of blood pressure and pulse interval was performed hourly in 6-week-old animals over 24 h. From these data, baroreflex sensitivity (BRS) was calculated by linear regression of spontaneous fluctuations of blood pressure and corresponding changes of pulse interval. Baroreflex sensitivity was lower in pre-hypertensive TGR rats than in SPRD rats, and the reduction was restricted to the daily resting period. In both strains, NOx excretion showed circadian rhythmicity, with peak values during the activity period at night. Interestingly, excretion of NOx was reduced during the resting period in 5-week-old TGR rats prior to the development of hypertension. Impairment of NO synthesis and baroreflex function precede the development of hypertension in TGR rats. The reduction of both parameters was restricted to the resting period and, therefore, could be involved in the development of the inverse circadian blood pressure profile of TGR rats.
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PMID:Reduced baroreflex sensitivity and blunted endogenous nitric oxide synthesis precede the development of hypertension in TGR(mREN2)27 rats. 1137 63

Blood pressure variability is buffered by at least two mechanisms: the arterial baroreceptor reflex and nitric oxide (NO). Only recently is the importance of blood pressure variations on cardiovascular control being investigated. Here we report of a study performed in conscious dogs, in which renovascular hypertension was induced. Reduction of renal arterial pressure (RAP) to 85 mmHg for 24 h elicited profound hypertension by 60 mmHg (vs. control: 110 +/- 3 mmHg; P < 0.01). This was accompanied by reduced volume and sodium excretion (-48% of control, P < 0.01 and -80% of control, P < 0.01, respectively) and augmented renin release by more than two-fold (P < 0.01). This intervention was compared with a protocol in which RAP was reduced to the same mean value, however, RAP oscillated by +/-10 mmHg at 0.1 Hz. This manoeuvre led to a transient increase in NO3 excretion in urine (P < 0.01), blunted antidiuresis (-14% of control) as well as antinatriuresis (-40% of control) and attenuated the increased renin release by 30% (P < 0.05). In consequence, the magnitude of blood pressure increase was only half as high as that observed during static reduction of RAP (P < 0.01). It is concluded that blood pressure oscillations to the kidney have a profound influence on water and electrolyte balance and on renin release, which alleviates the onset of Goldblatt hypertension.
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PMID:Nitric oxide and the role of blood pressure variability to the kidney. 1167 25

Cyclosporin-induced hypertension and endothelial dysfunction have been attributed to the effects of cyclosporin on factors controlling vasomotor tone. Endothelial nitric oxide (NO) regulates basal vasodilation, and an NO-mediated protective mechanism from cyclosporin-induced vasoconstriction has been proposed. In transplanted patients with cyclosporin-induced hypertension, we have recently demonstrated upregulation of the NO system and superoxide and free radical overproduction, which, by increasing NO metabolism, could induce hypertension, vascular remodeling and chronic rejection. In the present work, we have evaluated endothelial constitutive NO synthase (ecNOS), transforming growth factor beta and heme oxygenase-1 (protective against oxidative stress), mRNA production and plasma NO metabolites, peroxynitrite and antioxidant power in 15 kidney transplanted patients before and after 4 months of treatment with carvedilol alpha 1-beta-blocker and potent antioxidant. Our aim was to study the efficacy of the reduction of oxidative stress on complications such as endothelial dysfunction and fibrogenesis. Monocyte ecNOS and plasma NO metabolites remained higher versus those of control subjects and were unchanged by carvedilol, while antioxidant power and heme oxygenase-1 mRNA production increased. Peroxynitrite, as well as transforming growth factor beta mRNA, were reduced by carvedilol. It also normalized blood pressure. In conclusion, carvedilol reduces oxidative stress and normalizes blood pressure; ecNOS remains upregulated while mRNA for transforming growth factor beta, a key fibrogenic cytokine, is reduced by carvedilol, which seems to preserve protective mechanisms such as NO and heme oxygenase-1 against long-term complications of oxidative stress, e.g., endothelial dysfunction, fibrogenesis and chronic rejection.
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PMID:[Arterial hypertension and oxidative stress induced by cyclosporin. Effect of carvedilol]. 1168 56

In the present work, we have examined the effects of selective inhibition of the inducible isoform of nitric oxide synthase (iNOS) in rat medulla by aminoguanidine (AG) on the arterial pressure of Dahl salt sensitive (DS), Dahl salt-resistant (DR) and Sprague Dawley (SD) rats by chronic in vivo hemodynamic experiment, the effect of sodium chloride (NaCl) or NaCl plus AG infusion on urinary nitrate/nitrite (urinary NO3/NO2 UNO(x)), the end product of nitric oxide (NO), excretion, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and plasma renin activity (PRA). Furthermore, an iNOS activity assay was also made. The results showed that AG infusion significantly augmented the pressor response of DS and SD rats to high NaCl (8%) intake, and decreased GFR, ERPF and PRA of DS rats. In addition, in DS rats, renal medullary interstitial administration of high NaCl significantly elevated the iNOS activity of renal tissue, especially inner medulla and outer medulla, and greatly increased UNO(x) excretion. Therefore, it is concluded that inducible NOS is an important modulator of blood pressure in case of NaCl-induced hypertension.
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PMID:Role of renal medullary inducible nitric oxide synthase in the regulation of arterial pressure. 1196 77

Cyclosporine A (CsA) is an immunosuppressive agent, which also causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and rat aortic rings. Male rats weighing 250-300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal (ip) injection for 7 days. CsA administration produced a 42% increase (P < 0.001) in mean arterial pressure (MAP) which reached a plateau after 3 days. The level of both nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), decreased by 50% (P < 0.001), but the level of thromboxane A2 (TBXA2) increased by 75% (P < 0.001), in the urine. When 10(-9) M of CsAwas added acutely to intact aortic rings from untreated rats, NO2/NO3 production decreased by 83% (P < 0.011), but TBXA2 production increased by 86% (P < 0.001). The effects of CsA were reversed both in vivo and in vitro by pretreatment with propranolol (15 mg/kg/day ip), beta-adrenoceptor antagonist. There were no changes in MAP and tension in rats treated with prop alone. In addition, in aorta of rats that were treated with CsA ip for 7 days, CsA significantly activated protein kinase C (PKC) translocation. This suggests that PKC mediate, in part, CsA-induced hypertension. In summary, CsA inhibits endothelial NO formation, activate PKC, and increaseTBXA2 production, with resulting increase in MAP, and this changes can be overcome by pretreatment with propranolol.
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PMID:Nitric oxide in CsA-induced hypertension: role of beta-adrenoceptor antagonist and thromboxane A2. 1199 18

Choto-san is a formula used for the treatment of headache and vertigo. Recently it has often also been used for hypertension and dementia. One of the mechanisms involved is thought to be the improvement of blood circulation, but the details are still unclear. In this study, the effect of Chotosan was studied on nitric oxide (NO) function, hemorheological factors and endothelial function in stroke-prone spontaneously hypertensive rats (SHR-SP). Rats were given Choto-san in drinking water for eight weeks. Body weight, blood pressure, serum NO2-/NO3-, lipid peroxides, blood viscosity, erythrocyte deformability and endothelium-dependent/-independent relaxation were measured. The results indicated that Choto-san caused a decrease in blood pressure and an increase in erythrocyte deformability and NO function. Blood viscosity was not changed. Furthermore, endothelium-dependent relaxation by acetylcholine was significantly increased as compared to control. In this study, it was supposed that Choto-san had a protective effect on the endothelium. SHR-SP is a useful model for human brain stroke, and Choto-san showed a protective effect against cerebral vascular injury in the susceptible rat.
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PMID:Effects of Choto-san on hemorheological factors and vascular function in stroke-prone spontaneously hypertensive rats. 1199 55


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