Pressor resistance to vasopressin in sodium depletion, potassium depletion, and cirrhosis

Murray, B. M.; Paller, Mark S.

doi:10.1152/ajpregu.1986.251.3.r525

Cited by 23 publications

(18 citation statements)

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“…In our study, the hyporesponsiveness to methoxamine could be demonstrated only by the response in total peripheral resistance but not MAP. The failure to demonstrate a hyporesponsiveness to vasoconstrictors in terms of changes in MAP was also observed in a previous study by Murray and Paller (4,5) in cirrhotic rats. These authors estimated vascular sensitivity by only examining the pressure response, which is less sensitive than measurements of changes in vascular resistance that we performed in our study.…”

Section: Discussionsupporting

confidence: 78%

The Role of Nitric Oxide in the Vascular Hyporesponsiveness to Methoxamine in Portal Hypertensive Rats

et al. 1992

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This study examined whether an increased activity of the endothelium-derived relaxing factor, nitric oxide, may account for the hyporesponsiveness to vasoconstrictors in portal hypertension. We performed dose-response curves to methoxamine, an alpha-adrenoceptor agonist, with and without N omega-nitro-L-arginine, a specific inhibitor of nitric oxide synthesis, in experimental portal hypertension. Partial portal vein-ligated or sham-operated rats were pretreated with a continuous intravenous infusion of either N omega-nitro-L-arginine (50 micrograms.kg-1.min-1) or saline. Thirty minutes after starting the infusion of N omega-nitro-L-arginine or saline an infusion of methoxamine (10, 30 and 100 micrograms.kg-1.min-1) was added. Total peripheral resistance was calculated from mean arterial pressure and cardiac index. Repeated measurements of cardiac index were performed by a thermodilution technique. In portal vein-ligated rats pretreated with saline, the increase in total peripheral resistance after methoxamine infusion was significantly less than that of sham-operated rats (0.2 +/- 0.1 vs. 1.0 +/- 0.3, 0.6 +/- 0.1 vs. 1.6 +/- 0.3 and 3.7 +/- 0.5 vs. 6.1 +/- 0.7 mm Hg.ml-1.min.100 gm, p less than 0.05, methoxamine 10, 30 and 100 micrograms.kg-1.min-1, respectively). In the presence of N omega-nitro-L-arginine, the change in total peripheral resistance after methoxamine infusion was similar in both groups (p greater than 0.05). In conclusion, this study demonstrates that a vascular hyporesponsiveness to methoxamine is present in portal vein-ligated rats and that this hyporesponsiveness is reversed by blockade of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 78%

The Role of Nitric Oxide in the Vascular Hyporesponsiveness to Methoxamine in Portal Hypertensive Rats

et al. 1992

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“…BP was not significantly different between LC and NC at week 4, but LC had lower BP ( Figure 7) and heart rate (310 Ϯ 11 versus 360 Ϯ 7; P Ͻ 0.05) than NC at week 8 as previously reported (21,22). ETA blockade had no significant effect on BP in normal K ϩ and K ϩ -deficient rats.…”

Section: Etb Blockade Induced Hypertension In Normal Ksupporting

confidence: 76%

“…If this mechanism occurs in normokalemic animals, then endothelial dysfunction induced by hypokalemia may also contribute to the lack of BP elevation in hypokalemic rats administered the ETB antagonist. In addition, Murray et al (21) reported that the systemic vasculature is resistant to the pressor effect of AngII and vasopressin in chronic hypokalemia. Such pressor resistance to vasoconstrictors may also contribute to the absence of BP elevation in hypokalemic rats with ETB inhibition.…”

Section: Discussionmentioning

confidence: 99%

Endothelin A Receptor Blockade and Endothelin B Receptor Blockade Improve Hypokalemic Nephropathy by Different Mechanisms

Suga¹,

Yasui²,

Yoshihara

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Hypokalemia causes renal tubulointerstitial injury with an elevation in renal endothelin-1 (ET-1). It was hypothesized that hypokalemic tubulointerstitial injury is ameliorated by the blockade of ET-A receptors (ETA), whereas ET-B receptor (ETB) antagonism may exacerbate the injury, because ETB is thought to mediate vasodilation. Rats were fed a K ϩ -deficient diet alone (LC) or with an ETA-selective antagonist ABT-627 (LA) or an ETB-selective antagonist A-192621 (LB) for 8 wk. Control rats were on a normal K ϩ diet alone or with the ETA-selective or ETB-selective antagonists. The severity of hypokalemia was not significantly different among LA, LB, and LC. LC developed tubulointerstitial injury with an elevation of renal preproET-1 mRNA level. There was an increase in tubular osteopontin expression, macrophage infiltration, collagen accumulation, and tubular cell hyperplasia.ETA blockade significantly ameliorated all parameters for renal injury in the cortex without suppressing local ET-1 and ETA expression. By contrast, ETB blockade significantly reduced local ET-1 and ETA expression and improved the injury to a similar extent in the cortex. In the medulla, ETA or ETB blockade only partially blocked renal injury. ETA blockade did not affect BP in normokalemic or hypokalemic rats. ETB blockade induced a BP elevation with a decrease in urinary Na ϩ excretion in normokalemic but not in hypokalemic rats. These results indicate that ET-1 can mediate hypokalemic renal injury in two different ways: by directly stimulating ETA and by locally promoting endogenous ET-1 production via ETB. Thus, ETA as well as ETB blockade may be renoprotective in hypokalemic nephropathy.Endothelin-1 (ET-1) is a potent vasoconstrictive peptide originally isolated from endothelial cells, but it has since been shown to also be produced by non-endothelial cells, including renal epithelial cells and mesangial cells. ET-1 exerts its biologic actions through the activation of two different receptor isoforms. Whereas ET-A receptors (ETA) mediate vasoconstriction, mononuclear cell infiltration, and production of matrix proteins (1), ET-B receptors (ETB) on endothelial cells mediate endothelium-dependent vasorelaxation via nitric oxide (NO) and prostacyclin formation (2). Several other functions are also attributed to ETB, including regulation of renal sodium (Na ϩ ) and water excretion (3) and stimulation of ET-1 gene expression (4). Taking these biologic actions into consideration, it is not surprising to regard ET-1 as one of the important mediators for the progression of chronic renal injury (5,6). Urinary excretion of ET-1 as well as preproET-1 mRNA expression in mononuclear cells increases in patients with glomerulonephritis (7,8). Renal ET-1 levels and/or preproET-1 mRNA levels are upregulated in several experimental renal disease models of immune and nonimmune origins (5). The significance of ET-1 has been strengthened by the observation that glomerular and tubulointerstitial injury develop in preproET-1 transgenic mice despite ...

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“…For instance, in portal-veinligated rats, different laboratories have found that the mesenteric vessels show a hyporesponsiveness to vasoconstrictors [4,[7][8][9], but several papers agree that the aorta shows a normal response [23]. However, in cirrhotic rats with ascites, hyporesponsiveness to vasoconstrictors has been found in several vessel types [6,8,[24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Mesenteric hyporesponsiveness in cirrhotic rats with ascites: role of cGMP and K+ channels

et al. 2000

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A B S T R A C TThe mechanisms that mediate hyporesponsiveness to vasoconstrictors in liver cirrhosis are not completely established. In the present study we have explored the role of NO and potassium channels by studying the pressor response to methoxamine in rats with carbon tetrachlorideinduced cirrhosis with ascites. Experiments were performed in the isolated and perfused mesenteric arterial bed of control rats and of cirrhotic rats with ascites. Pressor responses to methoxamine, an α-adrenergic agonist, were analysed under basal conditions, after inhibition of guanylate cyclase with Methylene Blue (MB ; 10 µM), after inhibition of NO synthesis with N Gnitro-L-arginine (L-NNA ; 100 µM) and after blockade of potassium channels with tetraethylammonium (TEA ; 3 mM). Compared with those from controls, preparations from cirrhotic rats showed a lower pressor response to methoxamine (maximum : controls, 114.4p6.8 mmHg ; cirrhotic rats, 74.7p7.3 mmHg). Pretreatment with MB or L-NNA increased the responses in both groups, but without correcting the lower than normal response of the cirrhotic rats. Pretreatment with TEA alone did not modify the responses as compared with the untreated groups. Pretreatment with TEA plus MB or TEA plus L-NNA also potentiated the responses, and the responses of the cirrhotic animals were greater than those of the groups treated with MB or L-NNA alone. However, no treatment completely normalized the lower response of the mesenteries from cirrhotic animals, suggesting that factors other than NO and potassium channels also participate, although to a lesser degree, in the lower pressor response of the mesenteric arterial bed of animals with cirrhosis. These results confirm that NO and potassium channels are important mediators of the lower vascular pressor response of the mesenteric bed of cirrhotic rats with ascites. This effect seems to be mediated by the NO-dependent formation of cGMP and by the NO-dependent and -independent activation of potassium channels.

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Pressor resistance to vasopressin in sodium depletion, potassium depletion, and cirrhosis

Cited by 23 publications

References 0 publications

The Role of Nitric Oxide in the Vascular Hyporesponsiveness to Methoxamine in Portal Hypertensive Rats

The Role of Nitric Oxide in the Vascular Hyporesponsiveness to Methoxamine in Portal Hypertensive Rats

Endothelin A Receptor Blockade and Endothelin B Receptor Blockade Improve Hypokalemic Nephropathy by Different Mechanisms

Mesenteric hyporesponsiveness in cirrhotic rats with ascites: role of cGMP and K+ channels

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