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V Lahera

Publications and source records attributed to V Lahera.

At least 19 recordsLinked to original sources
PubMed2005

Effects of ovariectomy and growth hormone administration on body composition and vascular function and structure in old female rats.

UNLABELLED: Aging and estrogen-deprivation induce deleterious effects on body composition and vascular function in females. On the other hand, growth hormone (GH), whose production is reduced by age, exerts several vascular effects. The aim of this study was to investigate the effect of long-term estrogen deprivation and GH administration on body composition, vascular function and structure in aged female rats. METHODS: Twelve female Wistar rats were ovariectomized at 10 months of age. At 20 months of age, half of the ovariectomized rats were treated with GH for 4 weeks. The remaining ovariectomized rats animals and one group of six intact females were used as control groups. After the treatment period, animals were sacrificed and Specific Gravity Index (SGI) and periuterine fat weigh, as well as vascular reactivity and morphometry in aortic rings, were studied. RESULTS: No significant differences were found in SGI and periuterine fat weigh between ovariectomized and intact control rats. SGI was significantly increased by GH, and periuterine fat was reduced by the treatment. Dose-dependent relaxing responses to acetylcholine and isoproterenol were significantly diminished in ovariectomized rats as compared with intact animals, and GH treatment improved these responses. Ovariectomized animals showed significantly higher contracting responses to phenylephrine, acetylcholine + L-NAME and angiotensin-I than intact rats, and treatment with GH reduced them significantly. Media cross-sectional area was increased in ovariectomized rats as compared to intact animals, and GH reduced this area, but differences did not reach significance. CONCLUSION: GH has beneficial effects in body composition and endothelial function in old ovariectomized female rats.

Acetylcholine↗
PubMed2003

Body composition and vascular effects of growth hormone administration in old female rats.

Aging is associated with alterations in cardiovascular system and changes in body composition. The aim of this study was to investigate the effect of GH on body composition, vascular function and structure in old female rats. Old (20 months) and adult (4 months) female Wistar rats were used. One group of old animals was treated with GH (2 mg/kg/day) for four weeks. Periuterine fat weight, specific gravity index (SGI), dose response to Acetylcholine, Isoprenaline, Phenylephrine and Acetylcholine in the presence of L-NAME and vascular morphology in aortic rings, were studied. Old rats showed increased fat weight and decreased SGI (p<0.05) as compared to adult animals. GH reduced fat weight (p<0.05) and tended to increase SGI (NS). Old rats showed impaired vasodilatation to Acetylcholine and Isoprenaline (p<0.05), and GH improved these responses (p<0.05). Contraction response to Phenylephrine was higher in old than in adults rats (p<0.05), but GH did not show any effect. Contraction induced by Acetylcholine+L-NAME was higher in old rats than in adults, and GH tended to reduce this response, although not significantly. Aortic media area was increased in old rats, and GH reduced this parameter (p<0.05). In conclusion, GH shows beneficial effects on body composition, vascular function and morphology in old female rats.

Adipose Tissue↗
PubMed2001

Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits.

BACKGROUND: Numerous studies have shown that elevated plasma cholesterol can exacerbate renal disease. However, the effect of lipids on renal structure and vascular function in normal kidneys is less well established. Therefore, the aim of this study was to evaluate the impact of hypercholesterolaemia on glomerular structure and vascular reactivity of segmental arteries in rabbits. In addition, we also studied whether or not atorvastatin can prevent these structural and vascular alterations in hypercholesterolaemic rabbits. METHODS: Male New Zealand rabbits were fed either a normal rabbit chow or a diet containing 1% cholesterol and treated or not with atorvastatin (1 mg/kg/day) for 12 weeks. Dose-response curves to acetylcholine (10(-9)-10(-4) mol/l) and sodium nitroprusside (10(-9)-10(-4) mol/l) were studied in segmental arteries in the presence or absence of the thromboxane A2/PGH2 receptor antagonist ifetroban (10(-5) mol/l). Glomerular size and structure were also evaluated. RESULTS: Compared with control animals, hypercholesterolaemic rabbits presented glomerular hypertrophy and several types of injuries (capillary collapse, hyalinosis and alterations of Bowman's capsule), suggesting diffuse glomerulosclerosis. Segmental arteries also showed relaxing responses to acetylcholine and sodium nitroprusside which were lower than and similar to, respectively, those of control animals. The presence of ifetroban improved the acetylcholine response only in hypercholesterolaemic rabbits. Atorvastatin treatment prevented vascular and most glomerular changes associated with hypercholesterolaemia even in the presence of very high cholesterol levels. CONCLUSIONS: Atorvastatin exerts a protective effect on renal damage associated with hypercholesterolaemia even in the presence of deleterious levels of plasma cholesterol.

Acetylcholine↗
PubMed2001

Relevance of endothelium-derived hyperpolarizing factor in the effects of hypertension on rat coronary relaxations.

OBJECTIVES: To evaluate the relative participation of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in the relaxing responses induced by acetylcholine and isoproterenol in isolated coronary arteries from adult Wistar- Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male adult WKY rats and SHR were used in the study. Segments from left coronary arteries (approximately 350-380 microm internal diameter and 2 mm long) were mounted in an isometric myograph and pre-contracted with serotonin. Dose-response curves to acetylcholine and isoproterenol were carried out in absence and presence of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (LNAME), the inhibitor of the cyclo-oxygenase, indomethacin and KCI. Areas under the respective dose-response curves were used to calculate the approximate relative participation of NO, EDHF and prostanoids. RESULTS: Relaxations to either acetylcholine or isoproterenol were lower in SHR than in WKY rats. In WKY rats, presence of LNAME diminished (P< 0.05) relaxation to acetylcholine from 10(-9) to 10(-6) mol/l, and induced a contracting response at 10(-5) and 10(-4) mol/l of acetylcholine. Addition of indomethacin did not significantly affect dose-related relaxation to acetylcholine 10(-9) to 10(-6) mol/l in WKY rats, and reduced (P < 0.05) the contracting response observed at 10(-5) mol/l of acetylcholine. In SHR, addition of LNAME markedly reduced (P< 0.05) acetylcholine relaxations, but did not produce any contracting effect. Addition of indomethacin on top of LNAME slightly (P< 0.05) enhanced relaxing response to acetylcholine in SHR. Presence of LNAME in the media diminished (P < 0.05) relaxation to isoproterenol in both WKY rats and SHR. Addition of indomethacin on top of LNAME increased (P< 0.05) isoproterenol-relaxing response to levels similar to and higher than control conditions in WKY rats and SHR, respectively. Addition of KCI blunted both acetylcholine- and isoproterenol-relaxations in both groups. CONCLUSIONS: NO and EDHF are the main endothelium-derived relaxing factors underlying acetylcholine and isoproterenol relaxations in rat coronary arteries, respectively. EDHF reduction, and not only NO reduction play a key role in the diminished coronary relaxations induced by acetylcholine and isoproterenol in SHR. An arachidonic acid derivative with contracting activity released by acetylcholine and isoproterenol in a differential manner, could oppose the relaxing actions of NO and EDHF.

Acetylcholine↗
PubMed2000

The protective role of atorvastatin on function, structure and ultrastructure in the aorta of dyslipidemic rabbits.

Responses to both an endothelium-dependent (acetylcholine 10(-9)-10(-5) mol/l) and an endothelium-independent vasodilator (sodium nitroprusside 10(-10)-10(-6) mol/l) were studied in aortic rings from rabbits fed or not with a diet containing 0.5% cholesterol plus 14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg/kg/day). Morphometric and ultrastructure analyses were also performed. Rabbits fed the dyslipidemic diet presented higher plasma cholesterol and triglyceride concentrations than controls (P < 0.05). This was associated with intima-media thickening and, consequently, aortic stenosis (29 +/- 3%) since vessel cross-sectional area did not change. Endothelial cells presented numerous alterations in dyslipidemic rabbits. Atorvastatin treatment only reduced plasma levels in dyslipidemic rabbits (P < 0.05), which were nevertheless higher than those of controls. In addition, it prevented the reduction in acetylcholine relaxation in hypercholesterolemic animals. Atorvastatin administration also enhanced the response to acetylcholine in rabbits fed a control diet. Likewise, atorvastatin treatment reduced lesion area and consequently increased aortic lumen in dyslipidemic rabbits but did not modify media thickening. It also prevented the majority of the ultrastructural changes observed in endothelial cells. In conclusion, chronic atorvastatin treatment exerts a protective role in vascular function, structure and ultrastructure even in the presence of high cholesterol and triglyceride plasma levels.

Animals↗
PubMed2000

Effect of atorvastatin on endothelium-dependent constrictor factors in dyslipidemic rabbits.

Relaxations to acetylcholine and contractions to acetylcholine in the presence of the nitric oxide (NO) synthesis inhibitor (L-N(G)-nitroarginine methyl ester, L-NAME) were studied in aortic rings from rabbits fed either a control or a diet containing 0.5% cholesterol+14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg kg(-1) day(-1)). Rings were incubated with the endothelin (ET(A)) receptor antagonist BQ123, and/or the thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor antagonist ifetroban. In rabbits, high cholesterol and triglyceride plasma levels were associated with intimal thickening and blunted acetylcholine-relaxation as compared with controls. By contrast, acetylcholine+L-NAME response was higher. Incubation with either ifetroban or BQ123 increased acetylcholine-relaxation in both diet groups and it reduced the constrictor response only in dyslipidemic rabbits. Removal of endothelium reduced acetylcholine+L-NAME contraction in dyslipidemic rabbits, although increased it in control animals. Atorvastatin treatment reduced plasma lipid levels and lesion size in dyslipidemic animals. Likewise, it prevented acetylcholine-relaxation reduction. In addition, atorvastatin reduced constrictor response in dyslipidemic rabbits but only in rings with endothelium. Incubation with either ifetroban or BQ123 did not further modify these responses in atorvastatin-treated animals in any group. These data suggest that ET and TXA(2) availabilities seem to participate in the endothelial dysfunction associated with dyslipidemia. Atorvastatin treatment reduces intimal thickening and improves endothelial dysfunction in rabbits. This effect seems to be a consequence of its ability to act on ET and TXA(2) systems.

Animals↗
PubMed1999

Differential effects of losartan and doxazosin on vascular function in senescent spontaneously hypertensive rats.

We evaluated the effects of treatment for 12 weeks with 10 mg/kg/day of either losartan or doxazosin on vascular function in senescent spontaneous hypertensive rats (SHR). Both doxazosin and losartan reduced blood pressure, although the former was more effective. In contrast, both drugs reduced relative aortic weight and increased plasma nitrates to a similar extent. Losartan, but not doxazosin, increased the magnitude of the response to acetylcholine (10(-9) to 10(-5) mol/L). Both treatments increased relaxations to sodium nitroprusside (10(-10) to 10(-6) mol/L). These data show that losartan may possess advantages over doxazosin in improving vascular function in senescent SHR. This report emphasizes the importance of angiotensin II in vascular function alterations induced by aging in SHR.

Acetylcholine↗
PubMed1999

Effects of antihypertensive therapy on factors mediating endothelium-dependent relaxation in rats treated chronically with L-NAME.

OBJECTIVES: To evaluate the relative participation of endothelium-derived factors mediating relaxation in response to acetylcholine in isolated mesenteric vascular beds from rats treated chronically with N(G)-nitro-L-arginine methylester (L-NAME); and to compare the consequences of prolonged treatment with either an angiotensin converting enzyme inhibitor or a calcium channel blocker on the components of acetylcholine-induced relaxation in this vascular preparation. MATERIALS AND METHODS: Male Sprague- Dawley rats were treated for 8 weeks with L-NAME (40 mg/kg per day), quinapril (10 mg/kg per day), diltiazem (100 mg/kg per day), L-NAME + quinapril and L-NAME + diltiazem. Systolic blood pressure was estimated by a tail-cuff plethysmograph. Relaxing responses to acetylcholine (10(-12) to 10(-8) mol) in mesenteric vascular beds precontracted with phenylephrine (10(-5) mol/l) were studied in the presence and absence of L-NAME (10(-5) mol/l), L-NAME + indomethacin (10(-5) mol/l) or L-NAME + indomethacin + potassium chloride (6 x 10(-5) mol/l). The area under the dose- response curve was used to calculate the approximate participation of nitric oxide, prostaglandins or endothelium-derived hyperpolarizing factor in the acetylcholine-induced relaxation. RESULTS: Chronic administration of L-NAME increased blood pressure levels and vascular responsiveness to phenylephrine. Treatments with either quinapril or diltiazem reduced blood pressure levels and attenuated the increased response to phenylephrine. Relaxing responses to acetylcholine were similar in all groups, independently of the treatment received. The calculated participation of endothelium-derived hyperpolarizing factor in the acetylcholine-induced relaxation was higher than that of nitric oxide and prostaglandins in all groups, but was higher in L-NAME-treated than in untreated rats. In contrast, the participation of both nitric oxide and prostaglandins was higher in control than in L-NAME-treated rats. Quinapril increased the participation of prostaglandins in L-NAME-treated rats. Diltiazem increased the participation of nitric oxide in L-NAME-treated rats. CONCLUSIONS: The administration of L-NAME in Sprague-Dawley rats increased the production of endothelium-derived hyperpolarizing factor as a compensatory mechanism to maintain acetylcholine-induced relaxation. Antihypertensive therapy with either quinapril or diltiazem produced a selective redistribution of the endothelial factors mediating acetylcholine-induced relaxation.

Acetylcholine↗
PubMed1999

AT(1) receptor antagonism reduces endothelial dysfunction and intimal thickening in atherosclerotic rabbits.

The effects of angiotensin (AT)(1) receptor antagonists on functional and morphological alterations associated with atherosclerosis are not well known. The current study was performed to examine the long-term effects of valsartan (3 or 10 mg/kg per day for 10 weeks) on endothelial function and structural changes in aorta from rabbits fed with either a control diet or a cholesterol-enriched diet. Rabbits fed with the cholesterol-rich diet showed higher (P<0.05) plasma levels of cholesterol than did controls. Treatment with valsartan (3 or 10 mg/kg per day) did not alter plasma cholesterol levels or systolic arterial pressure in any group. Contractions induced by angiotensin II were comparable in both control and hypercholesterolemic rabbits and were markedly reduced by treatment with valsartan. Relaxations induced by acetylcholine were lower in hypercholesterolemic rabbits than in controls. Treatment with valsartan (3 or 10 mg/kg per day) enhanced (P<0.05) this response in hypercholesterolemic rabbits but not in controls. Lumen and media cross-sectional areas were comparable in control and hypercholesterolemic rabbits. Vessel area was higher (P<0.05) in hypercholesterolemic rabbits than in controls. Intimal lesion was 29.5+/-6% in cholesterol-fed rabbits and nonexistent in control rabbits. Treatments with 3 and 10 mg/kg per day valsartan reduced (P<0.05) intimal lesion to 2.4+/-0.7% and 2.7+/-0.9%, respectively, and increased lumen area in hypercholesterolemic rabbits. No changes in either vessel or media cross-sectional areas were observed in these animals. In summary, angiotensin II, through AT(1) receptors, appears to play a key role in the development of the vascular functional and structural changes associated with hypercholesterolemia. AT(1) receptor antagonists, besides their antihypertensive effects, could be an important therapeutic tool to reduce the development of atherosclerosis.

Angiotensin I↗
PubMed1999

Pressure natriuresis in nitric oxide-deficient hypertensive rats: effect of antihypertensive treatments.

Chronic inhibition of nitric oxide (NO) synthesis has been shown to result in arterial hypertension and an important blunting of the pressure diuresis and natriuresis response (PDN). The mechanisms mediating these abnormalities are not completely understood. In the present study, the role of several antihypertensive drugs to ameliorate these alterations was evaluated. The PDN relationships have been evaluated in rats chronically (8 wk) treated with the NO synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg per d in the drinking water). Appropriate groups of rats were simultaneously treated with the angiotensin II receptor blocker candesartan at a low (1.5 mg/kg per d) and high (2.5 mg/kg per d) dose, with the converting enzyme inhibitor captopril (60 mg/kg per d) and with the calcium channel blocker verapamil (100 mg/kg per d). Chronic treatment with L-NAME significantly elevated mean BP (163.6 +/- 6.5 mmHg versus 105.1 +/- 3.6 in controls), reduced GFR and renal blood flow (RBF), and shifted to the right the PDN responses. Chronic administration of low-dose candesartan, captopril, or verapamil prevented the arterial hypertension and improved renal hemodynamics, but these levels were not completely normalized. High-dose administration also improved renal hemodynamics but induced reduced BP below the levels of control animals. Despite the normalization of the elevated BP, the PDN responses of these hypertensive treated groups were not normalized, and the slopes of the respective diuretic or natriuretic responses were very similar to those of the hypertensive untreated rats. The results indicate that interruption or blockade of the renin-angiotensin system and calcium channel blockade are effective treatments for the NO-deficient arterial hypertension and renal vasoconstriction. However, the PDN responses are not normalized, and this finding suggests that the antihypertensive treatment is not enough to overcome the renal alterations associated with the chronic deficiency of NO.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

[Participation of endothelium-derived vasoconstrictor factors in arterial hypertension].

Vascular endothelial cells synthesize and release vasodilator (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor) and vasoconstrictor factors (thromboxane A2, prostaglandin H2, endothelin 1), which play a key role in the local regulation of vascular tone and participate in a crucial manner in the regulation of blood pressure. Hypertension has been shown to be associated with functional changes in the endothelium. In fact, decreased endothelium-dependent relaxations and increased endothelium-dependent contractions have been reported in both conduit arteries and resistance arteries obtained from various animal models of hypertension. During hypertension, the vessel wall experiences changes in the balance of the oxidative and the antioxidative enzyme system, resulting in increases in O2- release. This contributes to endothelial dysfunction by nitric oxide oxidation and the subsequent formation of peroxynitrite (ONOO-), a potent oxidant and potential mediator of vascular tissue injury. Finally, hypertension also allows the action or the production of vasoconstrictor factors such as endothelin 1 and thromboxane A2. As a consequence of these mechanisms, basal and/or stimulated nitric oxide availability is reduced, allowing vasoconstrictor systems, such as angiotensin II, sympathetic nervous system and others to over-express their actions. The mechanisms responsible for the alterations leading to endothelial dysfunction not only affect vasomotor tone, but also platelet aggregation and coagulation mechanisms.

Arachidonic Acid↗
PubMed1998

In vivo tissue specific modulation of rat insulin receptor gene expression in an experimental model of mineralocorticoid excess.

Insulin receptor (IR) gene expression at the mRNA level was investigated in hindlimb skeletal muscle, epididymal adipose tissue and in the liver of rats exposed to prolonged in vivo administration of deoxycorticosterone acetate (DOCA). Following treatment, plasma insulin levels were reduced while glucose levels increased compared to values in control rats. DOCA-treated animals showed an increase in blood pressure and a reduction in body weight. This treatment also induced hypokalemia and decreased plasma protein levels. Sodium levels were unaffected. Moreover, no differences in DNA and protein content or in the indicator of cell size (protein/DNA) were observed in the skeletal muscle or adipose tissue of animals. In contrast, there was a clear increase in the protein and DNA contents of the liver with no change in the indicator of cell size. Northern blot assays revealed 2 major IR mRNA species of approximately 9.5 and 7.5 Kb in the 3 tissues from control animals. DOCA treatment induced no change in the levels of either RNA species in skeletal muscle. However, a decrease of approximately 22% was detected in the levels of both species in adipose tissue whereas the liver showed an increase of 64%. These results provide the first evidence for an in vivo tissue-specific modulation of IR mRNA levels under experimental conditions of mineralocorticoid excess.

Adipose Tissue↗
PubMed1998

Factors involved in the effects of losartan on endothelial dysfunction induced by aging in SHR.

In the present study we investigated the effects of losartan (10 mg/kg/day; 12 weeks) on acetylcholine (Ach) induced relaxations in isolated mesenteric vascular beds (MVB) from adult and elderly spontaneous hypertensive rats (SHR). Experiments were done in absence or presence of either the NO synthesis inhibitor, L-NAME (10(-5) mol/liter), L-NAME + indomethacin (10(-5) mol/liter) or L-NAME + indomethacin + KCl (10(-5) mol/liter), to evaluate the participation of the factors (NO, PGs and EDHF, respectively) mediating Ach-relaxations. Systolic blood pressure levels were comparable in both groups. However, urinary nitrites excretion and Ach-response was lower in elderly than in adult SHR. The presence of L-NAME and L-NAME + indomethacin only reduced Ach-relaxations in untreated elderly SHR. Further addition of KCl to the perfusion media totally blunted Ach-relaxation in both groups. The calculated participation of endothelium-derived hyperpolarizing factor (EDHF) in Ach-relaxations was higher than that of nitric oxide (NO) and prostaglandins in both groups, although the EDHF component was lower in elderly when compared to adult SHR. Losartan treatment reduced blood pressure levels and enhanced dose-related Ach-relaxations and urinary nitrites in both groups. Presence of L-NAME and L-NAME + indomethacin blunted the enhancements induced by losartan on Ach-relaxations in both adult and elderly SHR. Further addition of KCl to the perfusion media totally blunted Ach-relaxation in both groups. The calculated participation of NO in Ach-relaxations was increased by losartan in both groups. Neither EDHF or prostanoids (PGs) components were clearly affected by losartan. In conclusion, (1) diminished EDHF availability accounts for the reduced Ach-relaxations produced by aging in MVB from SHR; (2) the enhancement of Ach-relaxations produced by losartan seems to be dependent on an increased NO availability; and (3) angiotensin II via angiotensin I type 1 receptor (AT1) plays an important role in the deleterious consequences of aging on endothelial function in SHR.

Acetylcholine↗
PubMed1998

Chronic treatment with losartan ameliorates vascular dysfunction induced by aging in spontaneously hypertensive rats.

OBJECTIVE: To evaluate the effects of prolonged treatment with losartan on endothelium-dependent and endothelium-independent relaxations of aortic rings from adult and senescent spontaneously hypertensive rats, and to clarify whether these effects were due to specific mechanisms of the drug or a consequence of its blood-pressure-lowering action. MATERIALS AND METHODS: Adult (aged 5 months) and senescent (aged 20 months) male spontaneously hypertensive rats were treated for 12 consecutive weeks with 10 mg/kg per day losartan. Systolic blood pressure and plasma concentration of nitrates were evaluated. We studied endothelium-dependent and endothelium-independent relaxations and response to angiotensin II of aortic rings from rats of each group. The direct effects of angiotensin II type 1 receptor antagonism on vascular reactivity of aortic rings from untreated adult and senescent rats that had been incubated beforehand with losartan were also studied. RESULTS: Losartan treatment comparably reduced blood pressure and increased plasma concentration of nitrates in rats of both age groups. Responses to acetylcholine and sodium nitroprusside were lower for rings from senescent than they were for rings from adult rats. Constrictor responses to angiotensin II were higher for rings from senescent than they were for rings from adult rats. Treatment with losartan increased the magnitude of relaxations in response to acetylcholine for rings from rats in both groups, but increased the magnitude of relaxations in response to nitroprusside only for rings from senescent spontaneously hypertensive rats. Incubation beforehand of aortic rings from untreated rats with losartan enhanced magnitude of relaxations in response both to acetylcholine and to nitroprusside only for rings from senescent spontaneously hypertensive rats. CONCLUSIONS: The consequences of aging for endothelium-dependent and endothelium-independent relaxations of rings from spontaneously hypertensive rats are ameliorated by losartan treatment, suggesting that angiotensin II plays a role via type 1 receptors. The effects of losartan on senescent spontaneously hypertensive rats were due not only to its blood-pressure-lowering action but also to the blockade of specific mechanisms derived from angiotensin II type 1 receptor antagonism, which might involve an increase in availability of NO.

Aging↗
PubMed1997

Nitric oxide, the kidney, and hypertension.

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.

Animals↗
PubMed1997

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients.

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.

Adult↗
PubMed1997

Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril.

BACKGROUND: Hypertension is associated with endothelial dysfunction characterized by decreased endothelium-dependent relaxations and increased endothelium-dependent contractions. Angiotensin converting enzyme inhibitors and thromboxane A2 receptor antagonists decreased the endothelium dysfunction in hypertensive animals. OBJECTIVE: To investigate the effects of prolonged treatment with losartan on endothelium-dependent and -independent relaxations and contractions in aortic rings from spontaneously hypertensive rats (SHR). MATERIAL AND METHODS: Male SHR aged 16 weeks were treated for 12 consecutive weeks either with 10 mg/kg losartan per day or with 60 mg/kg captopril per day administered via their drinking water. The systolic blood pressure was evaluated basally and during week 12. At the end of the treatment period, the vascular reactivity in aortic rings was studies. A group of rats treated with captopril was studies as a reference group. RESULTS: Losartan and captopril reduced the blood pressure significantly and comparably. Both drugs enhanced acetylcholine-induced relaxations and reduced the maximal contractile response to acetylcholine in the presence of NG-nitro-L arginine methyl ester (L-NAME). Contractile responses to phenylephrine, endothelin-l and U46619 were not affected by these treatments. Increased relaxing responses to superoxide dismutase were observed only in captopril-treated rats. Losartan reduced the contractile response to angiotensin II. By contrast this contractile response was elevated in rats treated with captopril. CONCLUSIONS: Prolonged antihypertensive treatments with losartan and captopril decreased the endothelial dysfunction in aortic rings from SHR not only by enhancing NO-dependent relaxations but also by reducing the contractions in response to an endothelium-derived contracting factor. The results further confirm that an endothelium-derived contracting factor plays a role in vascular dysfunction in SHR and the relationships between this factor and angiotensin II.

Acetylcholine↗