Biomedical subjects

T Quesada

Publications and source records attributed to T Quesada.

At least 19 recordsLinked to original sources

PubMed2006

Echocardiographic evaluation of the evolutionary changes after heart transplantation.

AIM: To undertake an evolutionary analysis of echocardiographic examinations carried out during follow-up of cardiac transplant patients. MATERIALS AND METHODS: The study included 193 consecutive patients transplanted between August 1998 and December 2004. We excluded pediatric, cardiopulmonary, and repeat transplants. Four echocardiographic examinations were analyzed per patient (first, second, third quarter and the last study carried out; average time from transplant: 1115 +/- 681 days). The total number of examinations was 772. The evaluated variables were thickness of walls and diameters of the cavities, systolic and diastolic functions, pericardial effusion, and number of rejections. RESULTS: The isovolumetric relaxation time showed reduced values during early echocardiography with subsequent increases during evolution (first echocardiogram: 92 +/- 16 vs final echocardiogram 101 +/- 16 ms; P < .0001). Right ventricular function showed initial deterioration with subsequent recovery (first echocardiogram: 16% vs final echocardiogram: 8%; P < .05); moreover, the existence of delayed malfunction of the right ventricle was correlated with a higher incidence of transplant rejection (P < .01). Pericardial effusion was initially present with a tendency to reduce over time (first echocardiogram: 58% vs final echocardiogram: 12%; P < .0001). There was no difference in the other variables. CONCLUSIONS: Cardiac transplant patients undergo evolutionary echocardiogram alterations that were mainly early and normalized as of the first quarter. The most usual changes in this period were restrictive isovolumetric behavior accompanied by some degree of depressed right ventricular function. Right ventricular malfunction during late evolution was correlated with a higher incidence of transplant rejection during follow-up.

Electrocardiography↗

PubMed2000

17beta-estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats.

In this study, we tested whether estrogen deficiency is associated with oxidative stress and decreased nitric oxide (NO) production, which could be responsible for an increased blood pressure in ovariectomized rats. Hemodynamic studies were performed on conscious, chronically instrumented rats. Chronic estrogen replacement on ovariectomized rats lowered blood pressure approximately 13 mmHg, from 119 +/- 3 mmHg in ovariectomized rats to 106 +/- 3 mmHg in ovariectomized-treated rats; it was also accompanied by an increase in cardiac index and vascular conductance, achieving hemodynamic values similar to those shown by sham-operated rats. N(G)-nitro-L-arginine methyl ester administration lowered significantly less the vascular conductance (0.14 +/- 0.01 vs. 0.22 +/- 0.03 and 0.26 +/- 0.01 ml. min(-1). mmHg(-1)/100 g; P < 0.05) in ovariectomized rats than in the sham-operated and estrogen-treated ovariectomized rats, respectively. Estrogen replacement prevented the lower plasma levels of nitrites/nitrates observed in ovariectomized rats. The lower plasma total antioxidant status and reduced thiol groups and the increase in plasma lipoperoxides presented in ovariectomized animals were reestablished with the estrogen treatment. These results show that estrogen administration decreases blood pressure and increases vascular conductance in ovariectomized rats. This effect may be related to an increase in NO synthesis and/or preventing oxidative stress, then improving endothelial function.

Animals↗

PubMed1999

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

Acetylcholine↗

PubMed1999

Role of angiotensin II in modulating the hemodynamic effects of nitric oxide synthesis inhibition.

This study examined the role of ANG II in modulating the increase of hematocrit and vascular permeability that follows nitric oxide (NO) synthesis blockade, that are contributing to the decrease in cardiac index (CI) in conscious, chronically catheterized rats. Pretreatment with losartan attenuated the N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced increase in total peripheral resistance by 26% and also blunted the fall in CI (28%) and stroke volume. L-NAME produced an increase in hematocrit (4.5%) and in (125)I-labeled albumin content in the heart and small intestine in untreated rats, but the increase was prevented in rats pretreated with losartan. Furthermore, L-NAME induced a transient increase of plasma protein concentration and tissue intestinal blood flow, which was abolished in rats given losartan. The results of the present study indicate that the systemic hemodynamic responses, the fall in plasma volume, and the increase in albumin escape observed after inhibition of NO synthesis are in part the consequence of unmasking the actions of endogenous ANG II. These data suggest a physiological role for NO by restraint of the vascular actions of the renin-angiotensin system.

Angiotensin II↗

PubMed1998

Protective effect of N-acetyl-L-cysteine on the renal failure induced by inferior vena cava occlusion.

BACKGROUND: Renal ischemia is produced during orthotopic liver transplantation when the inferior vena cava is clamped above the renal veins (inferior vena cava occlusion [IVCO]), and it often leads to postoperative renal failure. Although free radicals and nitric oxide (NO) have been implicated in the pathogenesis of ischemic renal failure, the effect of free radical scavengers in this model is unknown. METHODS: The effects of N-acetyl-L-cysteine (NAC), a free radical scavenger, on the acute renal failure that follows IVCO were evaluated in pentobarbital-anesthetized dogs. The effect of NO synthesis inhibition with NG-nitro-L-arginine methyl ester (NAME) was also studied. Renal vascular endothelial function was tested by infusing acetylcholine (Ach) into the renal artery before the ischemia and during reperfusion. RESULTS: Renal failure developed during IVCO and persisted during reperfusion in all groups. However, in NAC-pretreated dogs, the glomerular filtration rate recovered progressively, reaching 31% of basal preischemic values 150 min after reperfusion. During reperfusion, fractional excretion of sodium increased above preischemic values only in the control group, which indicates a beneficial effect of NAC and NAME on the tubular dysfunction observed during reperfusion. The renal response to Ach was abolished in control dogs and in animals given NAME during reperfusion, which indicates endothelial dysfunction. However, in NAC-pretreated dogs, the renal response to Ach was preserved during reperfusion. CONCLUSIONS: These results demonstrate that NAC ameliorates the renal failure and renal endothelial dysfunction induced by IVCO. This protective effect was abolished by NAME, which suggests that NO is involved in the beneficial effects of NAC. These data also suggest that the use of NAC could be beneficial in ameliorating the acute renal failure observed after orthotopic liver transplantation.

Acetylcholine↗

PubMed1998

Role of nitric oxide on the central hemodynamic response to acute volume expansion in the pregnant rat.

OBJECTIVES: Our hypothesis was that during pregnancy nitric oxide acts as mediator in the hemodynamic response to volume expansion. STUDY DESIGN: The study was performed on 12 rats on days 19 to 20 of pregnancy. Six rats were injected intravenously with hexamethonium bromide plus the inhibitor of nitric oxide synthase L-nitro-arginine methyl ester. For a control group, six rats were injected with hexamethonium bromide plus the L-nitro-arginine methyl ester vehicle. A volume expansion (1.2% body weight) was performed in both groups by intravenous infusion of bovine albumin (6%) solution. RESULTS: In the control group volume expansion induced a hyperdynamic circulation characterized by increased cardiac output, decreased total vascular resistance, and no change in arterial pressure; however, in the study group volume expansion induced a pressor response without hyperdynamic circulation. CONCLUSION: During pregnancy volume expansion induces a hyperdynamic circulatory state possibly mediated by nitric oxide release. A defect in the release of nitric oxide may be responsible for an inadequate hemodynamic response to volume expansion.

Animals↗

PubMed1998

Hemodynamic effect of 17 beta-estradiol in absence of NO in ovariectomized rats: role of angiotensin II.

Previous reports correlate plasma levels of estrogen with increased nitric oxide (NO) production. To investigate whether the hemodynamic effects of estrogens are mediated by NO, we compared the hemodynamic changes induced by 17 beta-estradiol (100 micrograms/kg) in the absence and presence of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). All protocols were performed in ovariectomized, conscious rats. Estradiol alone resulted in no significant changes in cardiac index (CI) or mean arterial pressure (MAP). However, in the presence of L-NAME, estradiol induced a significant increase in total peripheral resistance (TPR) of 37.3 +/- 11.7% and a decrease in CI of 27 +/- 4.9%, without changes in MAP. Previous blockade of angiotensin II AT1 receptors with losartan prevented any change in CI and TPR induced by 17 beta-estradiol in the presence of L-NAME. These observations suggest that NO is necessary to offset a vasoconstrictor action of angiotensin II, which is stimulated by estradiol administration.

Angiotensin II↗

PubMed1996

Role of protein kinase C in mesenteric pressor responses of rats with portal hypertension.

1. Hyporesponsiveness to vasoconstrictors is a characteristic abnormality of liver diseases of uncertain origin. In the present study, we have evaluated the involvement of protein kinase C (PKC) in the reduced pressor response to methoxamine (MTX) of a rat model of portal hypertension induced by partial portal vein ligation (PVL). Experiments were performed in the isolated and perfused mesentery. 2. The pressor response to MTX was reduced in PVL compared to that of control animals (Sham) and pretreatment with NG-nitro-L-arginine (L-NOARG, 10(-4) M) or removal of the endothelium potentiated the response of both groups. However, only removal of the endothelium completely eliminated the reduced pressor response to MTX of the PVL vessels. 3. Pretreatment of the mesentric vessels with calphostin C (10(-6) M), a PKC inhibitor, reduced the response to MTX of Sham to a level similar to that of untreated PVL vessels, but did not change that of PVL animals. 4. Mesenteric pressor responses to a PKC activator, phorbol 12,13-dibutyrate (PDBu), were similar in vessels from both PVL and Sham rats and pretreatment with L-NOARG or removal of the endothelium enhanced those responses while indomethacin (10(-5) M) decreased them. In all cases, the responses to PDBU were similar in PVL vessels compared to Sham. 5. These results indicate that the reduced pressor response to MTX of the mesenteric vascular bed of PVL rats is due to an endothelial alteration, compatible with an enhanced production of nitric oxide. The lack of response to calphostin C in PVL vessels suggests an impairment in agonist-induced PKC activation. Since direct activation of PKC induces a normal pressor response, it is concluded that the endothelial alteration interacts with the mechanism producing PKC activation, which results in a lower pressor response of the PVL mesenteric vaculature.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1996

Importance of nitric oxide and prostaglandins in the control of rat renal papillary blood flow.

The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of N omega-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8 +/- 3.6%, decreased papillary blood flow by 39.4 +/- 3.8%, and decreased renal blood flow by 47.4 +/- 1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2 +/- 2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n = 6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6 +/- 2.1% without significantly altering mean arterial ressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9 +/- 1.8%) and renal blood flow (49.8 +/- 6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure-renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure-papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure-papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure-blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.

Animals↗

PubMed1996

Chronic effects of nitric oxide and prostaglandin inhibition on pressure diuresis and natriuresis in rats.

The long-term interaction between nitric oxide (NO) and prostaglandins (PGs) in the pressure diuresis and natriuresis response has been studied. Experiments were performed in rats with chronic (8 weeks) inhibition of NO (NG-nitro L-arginine methyl Ester, L-NAME, 40 mg/kg/day) with or without simultaneous PGs synthesis blockade (indomethacin, 1 mg/kg/day). A time control group with no treatment was studied in parallel. At the end of this period, the animals were anesthetized and renal hemodynamics and excretion were studied at three levels of renal perfusion pressure (RPP; 100, 125 and 150 mm Hg). Renal blood flow, glomerular filtration rate, diuresis and natriuresis were lower at the three RPP levels in both L-NAME-treated groups than in the control or indomethacin-treated animals. Simultaneous administration of indomethacin plus L-NAME did not further modify the hemodynamic or excretory responses observed in the L-NAME-treated animals. These results show that chronic NO inhibition impairs the renal excretory response to changes in renal perfusion pressure, and simultaneous NO and prostaglandin synthesis inhibition does not reduce those responses further. It is concluded that, on a long-term basis, a preserved NO production, but not prostaglandin production, is critical for a normal pressure diuretic and natriuretic mechanism.

Animals↗

PubMed1995

Effect of N omega-nitro-L-arginine methyl ester on cardiac haemodynamic responses to adenosine infusion in conscious rats.

1. The aim of the present study was to evaluate the role of NO in the cardiovascular effects of adenosine in conscious rats. 2. Cardiac index was determinated by thermodilution. In a group of rats, three doses of adenosine were infused (i.v.) at a rate of 150, 300 and 450 micrograms/kg/min in the absence and in the presence of L-NAME (10 mg/kg). In a second group of rats, the experimental protocol was the same as that of the first group, except an infusion of methoxamine (50 micrograms/kg/min) was given during the second adenosine administration, instead of L-NAME. 3. In the absence of L-NAME or methoxamine, adenosine induced a dose-dependent decrease in mean arterial pressure and an increase in vascular conductance although adenosine did not affect cardiac index. 4. L-NAME administration attenuated the decreasing effect on the mean arterial pressure in response to the two lower doses of adenosine. In the presence of L-NAME, adenosine induced a significant increase in cardiac index from 18.7 +/- 1.5 to 29.1 +/- 1.9 and 26.2 +/- 1.4 ml/min/100 g. Administration of L-NAME significantly attenuated the adenosine-induced increase in vascular conductance. 5. Methoxamine infusion induced an enhanced response to adenosine infusion. In the presence of methoxamine, adenosine induced a significant greater decrease in mean arterial pressure, and increase in cardiac index and vascular conductance. 6. These results indicate that part of the cardiovascular effects of adenosine can be mediated by NO, since L-NAME administration partially blocked the adenosine-induced vasodilatation.

Adenosine↗

PubMed1995

Role of nitric oxide and prostaglandins in the regulation of blood pressure in conscious rats.

The present study was designed to investigate the possible role of endothelium-derived vasodilators, nitric oxide and prostaglandins, in the regulation of blood pressure during the presence and absence of the major pressor systems. Conscious rats were infused with a cocktail of inhibitors of the sympathetic nervous system, renin-angiotensin system, and V1 vascular receptor to vasopressin (achieved with hexamethonium, captopril, phentolamine, propranolol, and the V1 vasopressin (AVP) antagonist des-(CH2)5Tyr(Me)-AVP). The cocktail of vasoconstrictor inhibitors induced a marked fall of mean arterial pressure (MAP) from 109 +/- 2 to 52 +/- 2 mmHg (1 mmHg = 133.3 Pa) (n = 24). In animals with blockade, the specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginine methyl ester (L-NAME), induced a significant increase of MAP from 51 +/- 1 to 84 +/- 2 mmHg (n = 6). In the presence of indomethacin, a cyclooxygenase inhibitor, the pressor response to L-NAME was from 52 +/- 2 to 126 +/- 4 mmHg (n = 6). Neither indomethacin (n = 6) nor vehicle (n = 6) alone altered MAP. In intact animals without blockade, L-NAME caused a similar increase of MAP when it was injected alone (from 107 +/- 3 to 144 +/- 4 mmHg, n = 7) or with indomethacin (from 113 +/- 3 to 144 +/- 3, n = 6). Indomethacin alone (n = 8) did not change MAP. In conclusion, in the absence of the major pressor systems, the pressor effect of the inhibition of the production of endogenous nitric oxide and vasodilator prostanoid synthesis appears to be synergistic. These results suggest that these two endogenous vasodilators are involved in the maintenance of blood pressure.

Animals↗

PubMed1995

Involvement of renin-angiotensin system in the reduced pressure natriuresis response of hyperthyroid rats.

Previous studies have indicated that the pressure diuresis and natriuresis (PDN) response is greatly impaired in thyroxine-treated hypertensive rats. In the present study, we have examined the role of the renin angiotensin system (RAS) as a mediator of these alterations by characterizing the relationships between renal perfusion pressure and urine flow and sodium excretion in hyperthyroid rats acutely treated with a converting-enzyme inhibitor (captopril, 2 mg/kg) or an AT1 angiotensin II receptor blocker (losartan, 10 mg/kg). In the control animals, captopril did not change mean arterial pressure (MAP) or renal blood flow (RBF) but significantly decreased MAP and increased RBF and glomerular filtration rate in the hyperthyroid rats. Captopril did not change the PDN response of the control animals but improved significantly that of the hyperthyroid rats, although it was not completely normalized. Losartan also significantly improved renal hemodynamics and excretion in hyperthyroid rats. These results indicate that an increased intrarenal activity of the RAS is partly responsible for the blunted renal PDN mechanism of the hyperthyroid rats.

Animals↗

PubMed1995

Role of prostaglandins and nitric oxide in mediating renal response to volume expansion.

The objective of the present study was to examine, in anesthetized dogs, the possible interaction between prostaglandins (PG) and nitric oxide (NO) in mediating the renal response to an extracellular volume expansion (ECVE). The renal response to ECVE was examined during 1) intrarenal infusion of a PG synthesis inhibitor, 2) intrarenal administration of a NO synthesis inhibitor, and 3) simultaneous inhibition of PG and NO synthesis in the right kidney. Compared with the control group, the ECVE-induced increments in sodium excretion and fractional excretion of lithium were not affected by the PG synthesis inhibition. The NO synthesis inhibition did not induce changes in renal hemodynamics but reduced (P < 0.05) the ECVE-induced increments in sodium excretion and fractional excretion of lithium. When PG and NO synthesis were simultaneously inhibited in the right kidney during ECVE, there were no significant differences between the renal hemodynamics of both kidneys. However, compared with the left kidney, the ECVE-induced changes in sodium excretion and fractional excretion of lithium were reduced in the right kidney. The reduction of the natriuretic response to ECVE was greater (P < 0.05) than in the dogs where only NO synthesis was inhibited. Our results suggest a major interaction between NO and PG in mediating the renal hemodynamic and excretory responses to an increase in extracellular volume.

Animals↗

PubMed1994

Indomethacin does not modify the role of nitric oxide on blood pressure regulation of SHR.

1. The endothelium-dependent relaxation is impaired in spontaneously hypertensive rats (SHR) by the release of a vasoconstrictor prostanoid. We evaluated whether such a vasoconstrictor prostanoid is masking the vasodilatation induced by nitric oxide (NO). 2. For this we observed, in SHR, whether indomethacin (INDO) modified both the pressor response to the inhibition of NO biosynthesis with L-nitro-arginine methyl ester (L-NAME) and the acute hypotensive response to acetylcholine. 3. INDO did not modify basal mean arterial pressure (MAP), either the pressor response to L-NAME, or the depressor response to acetylcholine. 4. It shows that, in awake SHR, a vasoconstrictor prostanoid, did not seem to affect the acute regulatory function of NO on MAP.

Acetylcholine↗

PubMed1994

Cardiovascular effects of angiotensin II and vasopressin in intact awake rats.

1. In this study we evaluated, in intact awake rats, the effects of angiotensin II (AII) and vasopressin (AVP) on venous tone to explain their different hemodynamic effects. 2. Cardiac index (CI) was measured by thermodilution. AII and AVP were infused at the doses adjusted to increase mean arterial pressure 25, 50 and 70% above baseline. Lower doses of AVP than AII were necessary to increase mean arterial pressure at the same levels. 3. To study whether the different effects of AII and AVP on CI may be explained by their different actions on the venous system, changes in venous tone were evaluated by measuring mean circulatory filling pressure (MCFP) and determining the pressure gradient for venous return (PGVR). 4. AVP induced a decrease in CI from 32.5 +/- 2.2 to 23.1 +/- 1.7 and 15.4 +/- 0.8 ml/min/100 g (P < 0.01) with the second and third level of increase in afterload respectively, whereas AII at the same levels of afterload decreased CI from 34.8 +/- 1.3 to 28.3 +/- 2.3 and 23.4 +/- 1.7 ml/min/100 g (P < 0.01). Furthermore, the rise in total peripheral resistances (TPR) was greater with AVP than with AII at the highest level of afterload (P < 0.05). Heart rate significantly decreased more in the animals infused with AVP than with AII. 5. There were no changes in MCFP and PGVR with either AII or AVP. 6. These results indicate that in intact awake rats the larger fall in CI induced by AVP can not be explained only by a greater decrease in HR since at highest levels of afterload AVP decreased SV.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1994

Pressure-diuresis-natriuresis response in hyperthyroid and hypothyroid rats.

1. Renal responses to changes in renal perfusion pressure were studied in anaesthetized hyperthyroid (thyroxine, 300 micrograms day-1 kg-1) and hypothyroid (methimazole, 0.03% via drinking water) rats to determine whether an abnormality in the pressure-diuresis-natriuresis phenomenon is involved in the resetting of kidney function in these disorders. 2. There were no significant differences between control and hypothyroid rats with respect to the relationships between renal perfusion pressure and absolute or fractional water and sodium excretion. However, in hyperthyroid rats the pressure-diuresis-natriuresis mechanism was impaired. 3. Renal blood flow and glomerular filtration rate were well autoregulated and there were no differences between control and hypothyroid rats at every level of renal perfusion pressure. A significantly lower glomerular filtration rate was observed in hyperthyroid rats when data were expressed per gram kidney weight, but glomerular filtration rate was similar to that of control rats when normalized by body weight. 4. The shift in the pressure-diuresis-natriuresis response of hyperthyroid rats is mainly due to an increase in tubular reabsorption. Blunting of the renal pressure-diuresis-natriuresis mechanism in hyperthyroid rats may represent the functional resetting of the kidney necessary for sustained hypertension. However, a normal pressure-natriuresis response was observed in hypothyroid rats, in which blood pressure was markedly reduced.

Animals↗

PubMed1994

Increased endothelium-dependent renal vasodilation in cirrhotic rats.

We have evaluated the renal blood flow (RBF) response of cirrhotic rats to endothelium-dependent [acetylcholine (ACh)] and -independent [sodium nitroprusside (NP)] vasodilators. In anesthetized rats, ACh dose dependently increased RBF, but the response of the cirrhotic rats (n = 6) was significantly higher than that of the controls (n = 6). NP also increased RBF in a dose-dependent manner, but there were no differences between both groups. NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg i.v.) significantly reduced the responses to ACh in both groups, but those of the cirrhotic rats were still higher than those of the controls. In experiments performed in isolated perfused kidneys, preconstricted with phenylephrine, dose-response curves for ACh and NP were obtained in the presence of indomethacin. Both ACh and NP decreased renal perfusion pressure dose dependently, but only the response of the cirrhotic rats (n = 5) to ACh was significantly higher than that of the controls (n = 5). L-NAME (100 microM) significantly reduced the responses to ACh and increased those of NP and abolished the differences between groups, except at the high dose of ACh. These results demonstrate an elevated endothelium-dependent vasodilator response in the cirrhotic kidney, which is eliminated by combined prostaglandin and nitric oxide (NO) synthesis inhibition and suggest that increased intrarenal activity of NO may be contributing to the renal alterations of liver cirrhosis.

Acetylcholine↗