Search

Substrate use switches from fatty acids toward glucose in pressure overload-induced cardiac hypertrophy with an acceleration of glycolysis being characteristic. The activation of AMP-activated protein kinase (AMPK) observed in hypertrophied hearts provides one potential mechanism for the acceleration of glycolysis. Here, we directly tested the hypothesis that AMPK causes the acceleration of glycolysis in hypertrophied heart muscle cells. The H9c2 cell line, derived from the embryonic rat heart, was treated with arginine vasopressin (AVP; 1 [micro]M) to induce a cellular model of hypertrophy. Rates of glycolysis and oxidation of glucose and palmitate were measured in nonhypertrophied and hypertrophied H9c2 cells, and the effects of inhibition of AMPK were determined. AMPK activity was inhibited by 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo-[1,5- a]pyrimidine (compound C) or by adenovirus-mediated transfer of dominant negative AMPK. Compared with nonhypertrophied cells, glycolysis was accelerated and palmitate oxidation was reduced with no significant alteration in glucose oxidation in hypertrophied cells, a metabolic profile similar to that of intact hypertrophied hearts. Inhibition of AMPK resulted in the partial reduction of glycolysis in AVP-treated hypertrophied H9c2 cells. Acute exposure of H9c2 cells to AVP also activated AMPK and accelerated glycolysis. These elevated rates of glycolysis were not altered by AMPK inhibition but were blocked by agents that interfere with [Ca.sup.2+] signaling, including extracellular EGTA, dantrolene, and 2-aminoethoxydiphenyl borate. We conclude that the acceleration of glycolysis in AVP-treated hypertrophied heart muscle cells is partially dependent on AMPK, whereas the acute glycolytic effects of AVP are AMPK independent and at least partially [Ca.sup.2+] dependent. cardiac hypertrophy; energy metabolism; glucose utilization

Since the neurohypophyseal hormone 8-arginine vasopressin (AVP) is involved in cardiovascular tissue hypertrophy and myocyte differentiation, it is possible that local AVP plays a role in heart maturation. AVP-specific RIA, RT-PCR, and immunoblot measurement of AVP receptors (VR) were used to investigate heart tissues from newborn and adult rats. To test AVP's role in differentiation and specialization into ventricle-like cardiomyocytes, we studied GFP-P19Cl6 stem cells, which express green fluorescence protein (GFP) reporter under transcriptional control of the myosin light chain-2v promoter. [VR.sub.1] transcripts and proteins were higher in adult than in newborn rat hearts. In contrast, [VR.sub.2] increased from postnatal day 1 to 5 and was barely detected in the adult rat heart. In cardiomyocytes expressing troponin C, immunofluorescence revealed [VR.sub.2] and [VR.sub.1]. Intracellular cAMP increased 6.5- and 8.9-fold in response to the selective [VR.sub.2] agonist 1-desamino-8-D-AVP (DDAVP) after 1 and 24 h, respectively. Cardiac AVP was high in 1-and 5-day-old (330 [+ or -] 26 and 276 [+ or -] 53 pg/mg protein, respectively) but low in 66-day-old (98 [+ or -] 15 pg/mg protein) rats. AVP immuno-staining was detected in the tunica adventitia and endothelium of the coronary vessels. The possible role of AVP in cardiomyogenesis was indicated by DDAVP-AVP-dependent differentiation of GFP-P19Cl6 stem cells into contracting cells displaying GATA-4, a cardiacspecific marker, and ventricle-specific myosin light chain. Together, it is suggested that the AVP system is implicated in postnatal cardiac maturation. vasopressin; heart maturation; vasopressin receptors: immunochemistry; cardiomyocyte differentiation

Arginine vasopressin (AVP) plays a central role in water balance. In principal cells of the collecting duct system, AVP controls the expression of several genes, including aquaporin-2. Because nitric oxide (NO) participates in the regulation of water reabsorption by the collecting duct system, we analyzed the effect of AVP on the expression of NO synthase (NOS) isoforms in the kidney. Rats were either water restricted or water loaded to modify the circulating AVP levels, and expressions of NOS isoforms were assessed by Western blot analysis. In water-restricted rats, endothelial NOS (eNOS) expression increased in the outer medulla, and neuronal NOS (nNOS) expression rose in both the outer medulla and the papilla. Conversely, water loading induced a decrease in expression of nNOS in the outer medulla and papilla but did not alter eNOS expression. Oral administration of the specific V2-receptor antagonist SR-121463B decreased nNOS expression in the outer medulla and papilla but did not alter eNOS expression levels. Finally, the very low nNOS expression levels observed in AVP-deficient Brattleboro rats was restored by AVP infusion for I wk. Thus AVP specifically increases nNOS expression levels in the renal outer medulla and papilla. Because nNOS is specifically expressed in principal cells of the collecting duct system, the stimulation of nNOS expression by AVP may participate in the control of water reabsorption. principal cells; aquaporin-2; collecting duct; nitric oxide synthase

The role of G protein-coupled receptors and their ligands in intestinal epithelial cell signaling and proliferation is poorly understood. Here, we demonstrate that arginine vasopressin (AVP) induces multiple intracellular signal transduction pathways in rat intestinal epithelial IEC-18 cells via a [V.sub.1A] receptor. Addition of AVP to these cells induces a rapid and transient increase in cytosolic [Ca.sup.2+] concentration and promotes protein kinase D (PKD) activation through a protein kinase C (PKC)-dependent pathway, as revealed by in vitro kinase assays and immunoblotting with an antibody that recognizes autophosphorylated PKD at [Ser.sup.916]. AVP also stimulates the tyrosine phosphorylation of the nonreceptor tyrosine kinase proline-rich tyrosine kinase 2 (Pyk2) and promotes Src family kinase phosphorylation at [Tyr.sup.418], indicative of Src activation. AVP induces extracellular signal-related kinase (ERK)-1 ([p44.sup.mapk]) and ERK-2 ([p42.sup.mapk]) activation, a response prevented by treatment with mitogen-activated protein kinase kinase (MEK) inhibitors (PD-98059 and U-0126), specific PKC inhibitors (GF-I and Ro-31-8220), depletion of [Ca.sup.2+] (EGTA and thapsigargin), selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (tyrphostin AG-1478, compound 56), or the selective Src family kinase inhibitor PP-2. Furthermore, AVP acts as a potent growth factor for IEC-18 cells, inducing DNA synthesis and cell proliferation through ERK-, [Ca.sup.2+]-, PKC-, EGFR tyrosine kinase-, and Src-dependent pathways. arginine vasopressin; protein kinase D; protein kinase C; Src; proline-rich tyrosine kinase 2; intestinal epithelial proliferation

Peritubular AVP regulates bicarbonate reabsorption in cortical distal tubule via [V.sub.1] and [V.sub.2] receptors. Am J Physiol Renal Physiol 282: F256-F264, 2002; 10.1152/ajprenal.00056.2001. Peritubular arginine vasopressin (AVP) regulates bicarbonate reabsorption in the cortical distal tubule via [V.sub.1] and [V.sub.2] receptors. The dose-dependent effects of peritubular AVP on net bicarbonate reabsorption ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) were evaluated by stationary microperfusion of in vivo early (ED; distal convoluted tubule) and late distal (LD; connecting tubule and initial collecting duct) segments of rat kidney, using double-barreled [H.sup.+]-sensitive, ion-exchange resin/reference (1 M KCl) microelectrodes. AVP ([10.sup.-11] M) perfused into peritubular capillaries increased [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], compared with basal levels during intact capillary perfusion with blood, in ED and LD segments. AVP ([10.sup.-9] M) also increased [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] in both segments, but the effect of AVP ([10.sup.-11] M) was significantly higher. A specific [V.sub.1]-receptor antagonist alone or with AVP ([10.sup.-11] or [10.sup.-9] M) reduced [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] below basal levels. A specific [V.sub.2]-receptor antagonist alone or plus AVP ([10.sup.-11] M) did not affect [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] but increased AVP ([10.sup.-9] M)-mediated stimulation. 8-Bromoadenosine 3',5'-cyclic monophosphate alone reduced [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] below basal levels and also reduced AVP ([10.sup.-11] M)-mediated stimulation. (Deamino-[Cys.sup.1], D-[Arg.sup.8]) vasopressin (a [V.sub.2]-selective agonist) also reduced [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] below basal levels. These results show that peritubular AVP stimulates [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] in ED and LD segments via basolateral [V.sub.1] receptors and that basolateral [V.sub.2] receptors have a dose-dependent inhibitory effect mediated by cAMP. The data also indicate that endogenous AVP stimulates distal [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] via basolateral [V.sub.1] receptors. arginine vasorpressin; distal bicarbonate reabsorption

Experiments were performed on homozygous Brattleboro rats, which lack the arginine vasopressin (AVP), to examine the possibility of an AVP-independent regulation of aquaporin 2 (AQP2) mRNA gene expression in these rats. Antidiuresis and expressed AQP2 mRNA and AQP2 protein were found in the renal medullary of the rats after exogenous administration of 1-deamino-8-D-AVP. Findings also indicated the absence of an AVP-independent mechanism for upregulating AQP-2 gene expression.

The inhibition of the normal increase in plasma arginine vasopressin (AVP) induced by an intragastric NaCl infusion through hepatic denervation has been studied on Wistar-Kyoto rats subjected to either hepatic denervation or sham operation. Results indicate that the intragastric infusion of NaCl significantly elevated plasma AVP in sham-operated and hepatic-denervated rats. This finding suggests that hepatic osmoreceptors do not influence plasma AVP level due to intragastric NaCl.

The role played by arginine vasopressine (AVP) in the regulatory volume decrease (RVD) of astrocytes has been studied by using 3-O-((super 3)H)-methyl-D-glucose to determine water space. AVP produces pressor and antidiuretic responses by the activation of two distinct types of vasopressin receptors. Results indicated that there was a significant increase in the volume of 3-O-((super 3)H)-methyl-D-glucose after 30 seconds of exposure to AVP treatment. The volume remained elevated above baseline at the fifth minute. This is in contrast to untreated cells, where complete RVD was reached after five minutes.

The role of arginine vasopressin (AVP) in the production of nitric oxide and cyclic guanosine monophosphate in rat glomerular mesangial cells (GMC) has been studied. Its influence on the expression of the mRNA and protein of inducible nitric oxide synthase in rat GMC has also been examined. Griess method, enzyme immunoassay, northern and western blotting were used in investigating the functions of AVP. Results indicated that AVP inhibited the nitric oxide produced by lipopolysaccharides and interleukin-1-beta in a dose- and time-dependent manner.

A study was conducted on the phosphorylation of aquaporin 2 (AQP2) in rat renal tissues. AQP2 is a protein that facilitates arginine vasopressin (AVP)-modulated apical water transport in the renal collecting duct and maintains a phosphorylation site for cyclic adenosine monophosphate-dependent protein kinase A at Ser256. The findings indicated that AVP regulates the phosphorylation of Ser256 of AQP2 and possibly water permeability in collecting duct cells in kidneys.

A study was conducted to test whether arginine vasopressin (AVP) cannot stimulate chronic hypertension because of its inability to generate a sustained reduction of renal medullary blood flow. A pressure transducer was utilized to determine arterial pressure while medullary blood flows were obtained at 100 Hz using the Apollo DN3500 computer system. Results indicated that AVP cannot generate sustained elevations of arterial pressure because of its inability to minimize blood flow to the renal medulla.

The effect of bilateral subdiaphragmatic vagotomy and bilateral splanchnic denervation on the plasma arginine vasopressin and Fos immunoreactivity responses to intragastric hypertonic saline infusion in awake rats was investigated. Findings showed that either peripheral osmoreceptors project via both splanchnic and vagal afferents to mediate AVP release or that the observed response of plasma arginine vasopressin is caused by the activation of central osmoreceptors in the absence of measurable changes in plasma osmolality.

The effects of physiological elevations in arginine vasopressin (AVP) plasma levels on sympathetic activity and baroreflex function was analyzed in human subjects. Analysis of plasma AVP elevations in normal human subjects after the administration of angiotensin-converting enzyme inhibitors indicated the presence of normal baseline sympathetic nervous system activity based on plasma norepinephrine (NE) levels and plasma NE spillover. Furthermore, the responses of heart rate, forearm vascular resistance and systemic NE spillover to baroreceptor unloading was not affected by elevated AVP in normal human subjects.

Centrally released arginine vasopressin (AVP) has a role in the pressor effect of centrally administered angiotension (ANG) II. The pressor effects of centrally applied AVP and ANG II are not additive, and pressor response duration to the combined application of these peptides is significantly less compared to the separate application of AVP and ANG II. Studies with dogs show that ANG II and AVP interact to cause the termination of the pressor effect. The central pressor effect of ANG II is inhibited by the blockade of central V(sub 1) AVP receptors.

Oral administration of selective arginine vasopressin AVP V1 receptor antagonist OPC-21268 causes an increase in cardiac output and renal function while that of AVP V2 receptor antagonist OPC-31260 results in an increase in plasma renin activity, plasma levels and serum sodium concentration of AVP in dogs with congestive heart failure. AVP V1 receptor antagonist does not affect serum electrolytes and hormones while AVP V2 receptor antagonist induces water diuresis. Combined administration of both the receptor antagonists triggers additive metabolic and renal responses and supra-additive hemodynamic responses.

Acute restriction of the hypothalamic neurohypophyseal system present in patients with primary polydipsia can reduce osmotically-induced arginine vasopressin (AVP) release on reaction with hypertonic saline. The release of AVP is downregulated by acute overhydration in hypertonic human beings. Reduction in AVP release in patients with primary polydipsia leads to difficulty in distinguishing between patients with partial central diabetes insipidus and primary polydipsia.

The mechanism for the vasopressin-induced endothelium-dependent vasorelaxation was investigated using L-arginine and two of its analogues whichare known inhibitors the nitric oxide biosynthetic pathway. Nitric oxide synthase activity in dog basilar artery segments with intact or resected endothelium before and after vasopressin treatment. Results indicate that the vasopressin-induced vasorelaxation is mediated via the endothelial arginine pathway.

We tested the hypothesis that central arginine vasopressin (AVP) mediates postexercise reductions in arterial pressure (AP) and heart rate (HR). To test this hypothesis, nine spontaneously hypertensive rats (SHR) were instrumented with a 22-gauge stainless steel guide cannula in the right lateral cerebral ventricle and with a carotid arterial catheter. After the rats recovered, AP and HR were assessed before and after a single bout of dynamic exercise with the central administration of vehicle or the selective AVP [V.sub.1]-receptor antagonist d[([CH.sub.3]).sub.5] Tyr(Me)-AVP (AVP-X). AP and HR were significantly decreased below preexercise values with central administration of vehicle [P [is less than] 0.05, change ([Delta])-21 [+ or -] 4 mmHg and [Delta]-20 [+ or -] 6 beats/min, respectively]. In sharp contrast, after exercise with central administration of AVP-X, both AP ([Delta]+8 [+ or -] 5 mmHg) and HR ([Delta]+24 [+ or -] 9 beats/min) were not significantly different from preexercise values (P [is greater than] 0.05). Furthermore, AVP-X at rest did not significantly alter AP (181 [+ or -] 11 vs. 178 [+ or -] 11 mmHg, P [is greater than] 0.05) or HR (328 [+ or -] 24 vs. 331 [+ or -] 22 beats/min, P [is greater than] 0.05). Thus central blockade of AVP [V.sub.1] receptors prevented postexercise reductions in AP and HR. These data suggest that AVP, acting within the central nervous system, mediates postexercise reductions in AP and HR in the SHR. arginine vasopressin; arterial baroreflex resetting; cardiopulmonary baroreflex

The potent vasoconstrictor arginine vasopressin (AVP) is also a mitogen for mesangial cells. Treatment with AVP decreased transit time through the cell cycle. AVP-stimulated mesangial cell growth by activating both the Ras mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) cell signaling pathways. Both the selective PI3K inhibitor LY-294002 and the MAPK kinase (MEK) inhibitor PD-98059 inhibited AVP-stimulated mesangial cell proliferation. However, LY-294002 was more potent, indicating an important role for PI3K activation in AVP-stimulated mesangial cell proliferation. AVP appeared to exert its effect on MAPK and PI3K activation, as well as on cell proliferation, by activating the epidermal growth factor receptor (EGF-R). Pretreatment with the tyrphostin-derived EGF-R antagonist AG-1478 inhibited mesangial cell proliferation as well as the activation of extracellular signal-regulated kinase 1/2 (ERK1/2 or p42/ [p44.sup.MAPK]), and p70S6 kinase, a downstream effector of PI3K, providing evidence that MAPK and PI3K activation, respectively, occurred downstream of EGF-R activation. Treatment with rapamycin, an inhibitor of the p70S6 kinase activator mTOR, also resulted in growth inhibition, further suggesting the importance of the PI3K signaling pathway in AVP-induced proliferation. AVP treatment appeared to transactivate EGF-R by inducing tyrosine phosphorylation of the [Ca.sup.2+]/protein kinase C (PKC)-dependent nonreceptor tyrosine kinase, Pyk2, leading to Pyk2/c-Src association and c-Src activation. This was followed by association of c-Src with EGF-R and EGF-R activation. These data suggested that AVP-stimulated Pyk2 tyrosine phosphorylation to activate c-Src, thereby leading to EGF-R transactivation. mitogen-activated protein kinase; phosphatidylinositol 3-kinase; p70S6 kinase; Pyk2; c-Src

Effect of water deprivation and hypertonic saline infusion on urinary AQP2 excretion in healthy humans. Am J Physiol Renal Physiol 280: F860-F867, 2001.--Arginine vasopressin (AVP) mediates water transport in the renal collecting ducts by forming water channels of aquaporin-2 (AQP2) in the apical plasma membrane. AQP2 is excreted in human urine. We wanted to test the hypothesis that urinary excretion of AQP2 (u-AQP2) reflects the effect of AVP on the renal collecting ducts during water deprivation and hypertonic saline infusion in healthy subjects. Fifteen healthy subjects underwent a 24-h period of fluid restriction. Urine and blood samples were collected at timed intervals. Fifteen healthy subjects were given 7 ml/kg 3% hypertonic saline infusion for 30 min. Urine and blood samples were collected at timed intervals. During fluid restriction, the u-AQP2 rate increased from 3.9 (25th percentile: 3.1; 75th percentile: 5.2) to 7.6 (5.9-9.1; P [is less than] 0.001) ng/min, and the plasma AVP (p-AVP) level increased from 0.5 (0.4-0.6) to 3 (1.7-3.3) pmol/l. There was a positive correlation between the maximum change in u-AQP2 rate and the maximum change in p-AVP (r = 0.57, P [is less than] 0.03). During the infusion study, u-AQP2 rate was at maximum 90 min after the infusion [baseline: 4.5 ng/min (3.5-4.8); 90 min: 5 ng/min (4.5-6.0) P [is less than] 0.02]. p-AVP increased from 1.0 (0.9-1.1) to 1.5 (1.2-1.8; P [is less than] 0.002) pmol/]. There was a positive correlation between the maximum change in u-AQP2 rate and the maximum change in p-AVP (r = 0.83; P [is less than] 0.0001). It can be concluded that p-AVP and u-AQP2 are increased during thirst and hypertonic saline infusion and that u-AQP2 reflects the action of AVP on the collecting ducts. arginine vasopressin; healthy subjects; urinary output; aquaporin-2

Kakiya, Satoshi, Hiroshi Arima, Hisashi Yokoi, Takashi Murase, Yuko Yambe, and Yutaka Oiso. Effects of acute hypotensive stimuli on arginine vasopressin gene transcription in the rat hypothalamus. Am J Physiol Endocrinol Metab 279: E886-E892, 2000.--We investigated the baroregulation of arginine vasopressin (AVP) gene transcription in the supraoptic (SON) and paraventricular nuclei (PVN) in conscious rats by use of intronic in situ hybridization. Hemorrhage of 16 ml/kg body wt decreased mean arterial pressure (MAP) by 57% and increased both plasma AVP (control, 1.2 [+ or -] 0.3 pg/ml; 16 ml/kg body wt, 38.9 [+ or -] 3.2 pg/ml) at 10 min and AVP heteronuclear (hn)RNA levels (SON, 150%; PVN, 140% of control values) at 20 min. On the other hand, hemorrhage of 7 ml/kg body wt had no significant effect on MAP, plasma AVP, or the AVP hnRNA levels. To better understand the baroregulation, we also examined the effects of sodium nitroprusside (SNP), which induces hypotension without a change in blood volume. The subcutaneous injection of 2 mg/kg body wt SNP, which decreased the MAP by 60%, increased both plasma AVP (control, 1.6 [+ or -] 0.4 pg/ml; 2 mg/kg body wt, 8.1 [+ or -] 0.4 pg/ml) at 10 min and AVP hnRNA levels (SON, 150%; PVN, 140% of control values) at 30 min. The injection of 0.1 mg/kg body wt SNP, which reduced the MAP by 10%, failed to increase either the plasma AVP or AVP hnRNA levels. These results indicate that AVP gene transcription increases rapidly after both hypotensive hemorrhage and normovolemic hypotension. In addition, it is suggested that the set point for AVP synthesis in the baroregulation is similar to that for AVP release. heteronuclear RNA; supraoptic nucleus; paraventricular nucleus; in situ hybridization

Sarfaraz, Darya, and Cosmo L. Fraser Effects of arginine vasodepression on cell volume regulation in brain astrocyte in culture. Am J Physiol Endocrinol Metab 276: E596-E601, 1999.--Astrocytes initially swell when exposed to hypotonic medium but rapidly return to normal volume by the process of regulatory volume decrease (RVD). The role that arginine vasopressin (AVP) plays in hypotonically mediated RVD in astrocytes is unknown. This study was therefore designed to determine whether AVP might play a role in astrocyte RVD. With the use of 3-O-[[sup.3]H]methyl-D-glucose to determine water space, AVP treatment resulted in significantly increased 3-O-methyl-D-glucose water space within 30 s of hypotonic exposure (P = 0.0001) and remained significantly elevated above baseline (1.75 [micro]l/mg protein) at 5 min (P [is less than] 0.021). In contrast, in untreated cells, complete RVD was achieved by 5 min. At 30 s, cell volume with AVP treatment was 37% greater than in cells that received no treatment (2.9 vs. 2.26 [micro]l/mg protein, respectively; P [is less than] 0.006). The rate of cell volume increase (dV/dt) over 30 s was highly significant (0.038 vs. 0.019 [micro]l [multiplied by] mg [protein.sup.-1] [multiplied by] [s.sup.-1] in the AVP-treated vs. untreated group; P = 0.0004 by regression analysis). Additionally, the rate of cell volume decrease over the next 4.5 min was also significantly greater with vasopressin treatment (-dV/dt = 0.0027 vs. 0.0013 [micro]l [multiplied by] mg [protein.sup.-1] [multiplied by] [s.sup.-1]; P = 0.0306). The effect of AVP was concentration dependent with [EC.sub.50] = 3.5 nM. To determine whether AVP action was receptor mediated, we performed RVD studies in the presence of the [V.sub.1]-receptor antagonists benzamil and ethylisopropyl amiloride and the [V.sub.2]-receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP). Both [V.sub.1]-receptor antagonists significantly inhibited AVP-mediated volume increase by 40-47% (P [is less than] 0.005) whereas DDAVP had no stimulatory effects above control. Taken together, these data suggest that AVP treatment of brain astrocytes in culture appears to increase 3-O-methyl-D-glucose water space during RVD through [V.sub.1]-receptor-mediated mechanisms. The significance of these findings is presently unclear.

[V.sub.1] receptors in luminal action of vasopressin on distal [K.sup.+] secretion. Am J Physiol Renal Physiol 278: F809-F816, 2000.--Luminal perfusion with collected proximal fluid increases distal [K.sup.+] secretion compared with artificial solutions. Arginine vasopressin (AVP), present in luminal fluid, might be responsible for this observation. [K.sup.+] secretion rate ([J.sub.K]) was measured by [K.sup.+] -sensitive microelectrodes during paired luminal stationary microperfusion with control and AVP-containing 0.5 mM [K.sup.+] solutions. [J.sub.k] was 1.34 [+ or -] 0.35 (n = 24 tubules) nmol [multiplied by] [cm.sup.-2] [multiplied by] [s.sup.-1] during perfusion with [10.sup.-9] M AVP, against 0.90 [+ or -] 0.12 nmol [multiplied by] [cm.sup.-2] [multiplied by] [s.sup.-1] (n = 21) in control (P [is less than] 0.02). With [10.sup.9] M AVP + [10.sup.-6] M [Beta]-mercapto-[Beta]-[Beta]-cyclopenta- methylenepropionyl.sup.1] O-Me-[Tyr.sup.2]-[Arg.sup.8] vasopressin (MCMV), a specific peptide [V.sub.1]-receptor antagonist, [J.sub.K] was 0.36 [+ or -] 0.067 against 0.77 [+ or -] 0.10 (control; n = 9) nmol [multiplied by] [cm.sup.-2] [multiplied by] [s.sup.-1] (P [is less than] 0.01). With [10.sup.-6] M MCMV alone, [J.sub.K] was 0.37 [+ or -] 0.04 against a control of 0.62 [+ or -] 0.06 (n = 19) nmol [mutliplied by] [cm.sup.-2] [multiplied by] [s.sup.-1] (P [is less than] 0.01). A peptide [V.sub.2] antagonist had no such effect. In Brattleboro rats, which do not produce endogenous AVP, MCMV had no effect when given alone, although AVP still stimulated [J.sub.K]. In conclusion, luminal AVP stimulates distal [J.sub.K] significantly. The [V.sub.1] antagonist MCMV inhibits the effect of AVP but also reduces [J.sub.K] when given alone. This suggests that AVP acts luminally via [V.sub.1] receptors but also that there appears to be a background effect of endogenous AVP blocked by the antagonist. potassium; anti- [V.sub.1]; distal tubule; microperfusion