Influence of vasopressin on renal hemodynamics in conscious Brattleboro rats

Gellai, Miklos; Silverstein, J. H.; Hwang, Jaulang; Larochelle, F. T.; Valtin, Heinz

doi:10.1152/ajprenal.1984.246.6.f819

Cited by 37 publications

(34 citation statements)

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“…1 and 2, following the administration of CGP 29325, there was a latent period before Uosm reached the lowest sin system to the altered renal hemodynamics requires further study. The physiological siginificance of V1 receptors in the renal circulation is controversial (7,8,17). The present results demonstrated that renal hemodynamics do not respond to V1 blockade in anesthetized dogs, thereby suggesting a minor role for the vascular action of AVP in the renal vasculature.…”

Section: Discussioncontrasting

confidence: 42%

“…They used an AVP analogue that inhibits AVP actions at vascular receptor sites, decreased renal vascular resistance and increased RBF in Long Evans rats but not in rats with hereditary diabetes insipidus (7). Gellai et al reported that long-term treatment with physiological doses of AVP alters body fluid volume in association with increases in GFR and RBF, although acute intravenous administration did not alter the renal hemodynamics (17). However, Gellai noted that GFR fell substantially with no change in RBF when V1 and V2 antagonists were given together to conscious rats, although the V1 antagonists alone had no effects on RBF and GFR (8).…”

Section: Discussionmentioning

confidence: 99%

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Renal effects of specific antagonists of arginine vasopressin in dogs.

et al. 1991

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ABSTRACT-To investigate the effects on renal hemodynamics of specific antagonists of arginine vasopressin (AVP), CGP 29325 (d(CH2)5-D-Tyr(Et)VAVP), which has both anti-vasopressor and anti-antidiuretic activities against AVP, and CGP 25838E (d(CH2)5-Tyr(Me)AVP), which has only anti-vasopressor activity, were administered to normally hydrated anesthetized dogs, and the effects on renal function were examined. The pressor response and constriction of renal and mesenteric arteries induced by AVP were dose-dependently blocked by intravenous CGP 25838E. Following intrarenal arterial administration (i.r.a.) of CGP 29325 at 3,ug/min, water diuresis occurred and urine osmolality (Uosm) decreased to less than 250 mOsm/kg. Renal blood flow (RBF), glomerular filtration rate (GFR), and urinary sodium excretion (UNaV) remained unchanged. A higher dose (10,ug/min, i.r.a.) of CGP 29325 further decreased Uosm to about 110 mOsm/kg. Although arterial blood pressure (BP), GFR and UNaV remained unchanged, RBF decreased from the control value 3.7 ± 0.35 to 2.4 ± 0.40 ml/g•min. CGP 25838E (10,ug/min, i.r.a.) had no effect on renal hemodynamics and urine formation. When administered into the mesenteric artery, CGP 25838E (10,ug/min) increased mesenteric blood flow (MBF) from 199 ± 34 to 240 ± 40 ml/min without any alteration in blood pressure. We tentatively conclude that CGP 29325, at a lower dose, exerted anti-antidiuretic effects through a specific inhibition of V2 receptors, while the higher dose of CGP 29325 altered RBF, through yet to be determined mechanisms. The vasoconstrictive activity of AVP may contribute to the regulation of mesenteric circulation, but not to renal hemodynamics, in anesthetized dogs. pressor activity, while the latter mediates antidiuretic activity. In in vitro experiments, a V2 antagonist has been shown to specifically inhibit the AVP-dependent adenylate cyclase of human and animal kidneys in a competitive manner (4). A V1 receptor antagonist inhibits AVP induced smooth muscle contraction of the rat uterus (2). Antagonists which have an in vitro high specificity for V1 and/or V2 receptors may be effective agents for treating

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Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

Renal effects of specific antagonists of arginine vasopressin in dogs.

et al. 1991

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“…The objective of the present work, therefore, was to test this hypothesis. The major findings were as follows: (a) several dosages of the nitric oxide synthase inhibitor, NAME, acutely equalized effective renal plasma flow and renal vascular (18). One of the few conditions which does recapitulate the renal hemodynamic changes of pregnancy is chronic expansion of total body water produced by continuous administration of arginine vasopressin or oxytocin (reviewed in reference 19).…”

Section: Discussionmentioning

confidence: 99%

Acute blockade of nitric oxide synthase inhibits renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats.

Danielson¹,

Conrad²

1995

J. Clin. Invest.

140

102

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Because the kidneys are vasodilated and the endogenous production of nitric oxide is increased in gravid rats, we tested whether nitric oxide mediates the renal vasodilatory response to pregnancy. Chronically instrumented, conscious rats of gestational days 12-14 were studied concurrently with age-matched virgin control animals. GFR and effective renal plasma flow (ERPF) were determined by the renal clearances of inulin and para-aminohippurate before and during acute infusion of NW-nitro-L-arginine methyl ester (NAME; 2, 20, and 50 jag/min) or NG-monomethyl-L-arginine (100 jag/min). Baseline GFR and ERPF were significantly increased, and effective renal vascular resistance was decreased by 30-40% in gravid rats compared with virgin controls. During infusion of all three dosages of NAME and NG-monomethyl-L-arginine, effective renal vascular resistance, GFR, and ERPF were equalized in the pregnant and virgin rats (the only exception being GFR during the 20 jag/min NAME infusion). When compared with virgin rats, the gravid animals were more responsive to nitric oxide synthase inhibition, showing a significantly greater decline in GFR and ERPF and rise in effective renal vascular resistance at each timepoint during the infusion of inhibitor. To exclude the possibility that nonspecific renal vasoconstriction per se led to equalization of renal function in the two groups of rats, we investigated angiotensin II. In contrast to the results observed with nitric oxide synthase inhibitors, pregnant rats were less responsive to the renal vasoconstrictory effects of angiotensin II, such that the baseline differences in renal parameters measured before infusion of the hormone were increased during the infusion. To determine whether nitric oxide synthase was inhibited to a similar extent in gravid and virgin rats, aortic and renal cortical cGMP content was assayed ex vivo at the end of inhibitor infusion. The lower 2-pag/min dose of NAME consistently reduced cGMP content of these tissues to comparable levels in the two groups of rats. In conclusion, we suggest that Receivedfor publication 20 December 1994 and accepted in revised form 14 March 1995. nitric oxide mediates reduced renal vascular resistance and hyperfiltration during pregnancy in conscious rats. (J. Clin. Invest. 1995. 96:482-490.)

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“…One group of animals was not treated (control), and the other three groups received the vasopressin analog 1-desamino-8-D-arginine vasopressin (dDAVP) subcutaneously at a rate of 5 l/h (1.2 g/day) via osmotic minipumps, as previously described (34). This dose has been shown to produce plasma vasopressin levels comparable to those achieved in normal rats during water restriction (10). Animals from two of these dDAVP-treated groups were fixed after either 1 day (acute) or 8 days (chronic) dDAVP exposure.…”

Section: Methodsmentioning

confidence: 99%

Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells

Silberstein¹,

Bouley²,

Huang³

et al. 2004

American Journal of Physiology-Renal Physiology

142

145

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(AQP4) water channels exist as heterotetramers of M1 and M23 splice variants and appear to be present in orthogonal arrays of intramembraneous particles (OAPs) visualized by freeze-fracture microscopy. We report that AQP4 forms OAPs in rat gastric parietal cells but not in parietal cells from the mouse or kangaroo rat. Furthermore, the organization of principal cell OAPs in Brattleboro rat kidney is perturbed by vasopressin (arginine vasopressin). Membranes of LLC-PK1 cells expressing M23-AQP4 showed large, abundant OAPs, but none were detectable in cells expressing M1-AQP4. Measurements of osmotic swelling of transfected LLC-PK1 cells using videomicroscopy, gave osmotic water permeability coefficient (Pf) values (in cm/s) of 0.018 (M1-AQP4), 0.019 (M23-AQP4), and 0.003 (control). Quantitative immunoblot and immunofluorescence showed an eightfold greater expression of M1-over M23-AQP4 in the cell lines, suggesting that single-channel pf (cm 3 /s) is much greater for the M23 variant. Somatic fusion of M1-and M23-AQP4 cells (Pf ϭ 0.028 cm/s) yielded OAPs that were fewer and smaller than in M23 cells alone, and M1-to-M23 expression ratios (ϳ1:4) normalized to AQP4 in M1 or M23 cells indicated a reduced single-channel pf for the M23 variant. Expression of an M23-AQP4-Ser 111E mutant produced ϳ1.5-fold greater single-channel pf and OAPs that were up to 2.5-fold larger than wild-type M23-AQP4 OAPs, suggesting that a putative PKA phosphorylation site Ser 111 is involved in OAP formation. We conclude that the higher-order organization of AQP4 in OAPs increases single-channel osmotic water permeability by one order of magnitude and that differential cellular expression levels of the two isoforms could regulate this organization. water transport; freeze-fracture; LLC-PK1 cells; orthogonal arrays; intramembraneous particles THE MAMMALIAN FAMILY OF AQUAPORIN water channels consists of 12 known members, each with a specific tissue distribution and membrane localization pattern. However, the role of aquaporin-4 (AQP4) in water transport physiology is not well understood. AQP4 was the first aquaporin to be observed and identified in biological membranes, because when examined by freeze-fracture electron microscopy, it forms characteristic arrays of intramembraneous particles (IMPs) in the form of checkerboard aggregates or orthogonal arrays of intramembraneous particles (OAPs). These OAPs were described in various cell membranes long before a role in water permeability was suspected (3,18,27,31,32). The relationship of OAPs to water channels was first suggested by earlier studies showing that membranes that contained OAPs, including astrocytes, gastric parietal cells, and collecting duct principal cells were immunostained by an antibody raised against the whole AQP1 (then called CHIP28) protein (37). A different antibody raised against skeletal muscle OAP-containing membranes also recognized an ϳ30-kDa protein in these membranes (15,41). In this way, a protein initially called basolateral intrinsic membrane protein (BLIP) was ...

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Influence of vasopressin on renal hemodynamics in conscious Brattleboro rats

Cited by 37 publications

References 0 publications

Renal effects of specific antagonists of arginine vasopressin in dogs.

Renal effects of specific antagonists of arginine vasopressin in dogs.

Acute blockade of nitric oxide synthase inhibits renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats.

Membrane organization and function of M1 and M23 isoforms of aquaporin-4 in epithelial cells

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