Caffeine-induced natriuresis and diuresis via blockade of hepatic adenosine-mediated sensory nerves and a hepatorenal reflex

The hepatorenal reflex, activated by intrahepatic adenosine, is involved in the regulation of urine production in healthy rats and renal pathogenesis secondary to liver injury. Hepatic adenosine A1 receptors regulate the hepatorenal reflex. The aim of the present study was to evaluate whether caffeine mediates renal natriuresis and diuresis in healthy and diseased liver through this mechanism. Rats were anesthetized and instrumented to monitor systemic, hepatic, and renal circulation and urine production. Intrahepatic (intraportal but not intravenous) caffeine (5 mg·kg-1) increased urine flow (~82%) in healthy rats. This effect was abolished by liver denervation. Intraportal infusion of adenosine decreased urine production, and this response was abolished by intraportal but not intravenous caffeine. Liver injury was induced by intraperitoneal injection of thioacetamide (500 mg·kg-1), and functional assessment was performed 24 h later. Liver injury was associated with lower (~30%) glomerular filtration rate, lower (~18%) renal arterial blood flow, and lower urine production. Intraportal but not intravenous caffeine improved basal urine production and renal ability to increase urine production in response to saline overload. The liver-dependent diuretic effect of caffeine is consistent with the hypothesis for the adenosine-mediated mechanism of hepatorenal syndrome.     

Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

Renal adenosine A3 receptors in the rat: assessment of functional role

The functional roles of adenosine A3 receptors in the rat kidney were assessed for the first time with respect to A1 receptor-mediated responses. Utilizing a chronically instrumented conscious rat preparation, we tested renal excretory responses to acute administration of the A3 receptor antagonists 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1 ,4-(+)-dihydropridine-3,5-dicarboxylate (MRS-1191) and 9-chloro-2-(2-furyl)-5-phenylacetylamino-[1,2,4]-triazolo[1,5-c]qu inazoline (MRS-1220) with reference to the effects of the A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The intravenous administration of DPCPX resulted in significant increases in fluid and sodium excretions without affecting glomerular filtration rate (GFR). This suggests that DPCPX-induced diuretic and natriuretic responses are related to decreased tubular reabsorption. However, neither MRS-1191 nor MRS-1220 alone affected fluid or sodium excretions, or GFR, indicating lack of an effect of either compound on renal function. On the other hand, the co-administration of MRS-1220 with DPCPX abolished both the diuretic and natriuretic responses to DPCPX, being suggestive of antagonism between these two compounds. MRS-1191, however, did not affect the DPCPX-induced fluid and sodium excretions. Neither the A1 nor the A3 receptor antagonists altered potassium excretion individually or in combination. The data suggest that while adenosine A1 receptors are involved in the regulation of renal fluid and sodium transport, A3 receptors do not appear to have a major role in regulation of renal excretory function under baseline physiological conditions.     

The effect of nitrendipine on renal haemodynamics and tubular reabsorption and its neural control in anaesthetised rats with chronic renal failure.

This study examined the influence of a calcium channel antagonist, nitrendipine, on blood pressure and kidney function in a rat model of chronic renal failure. Additionally, the effects of low frequency renal nerve stimulation were studied in the presence and absence of nitrendipine. Male Wistar rats were fed a diet high in adenine for 4 weeks and then acutely anaesthetised and prepared for renal functional measurements. Blood pressure was elevated but renal blood flow and glomerular filtration rate were reduced, between 30 to 50%, urine flow and absolute sodium excretion were lower and fractional sodium excretion was two to three times higher than in normal rats. Nitrendipine (0.25 microg/kg/min i.v.) decreased blood pressure at 114+/-7 mm Hg, by 11% (P<0.05), increased left renal blood flow, at 1.3+/-0.2 ml/min(-1) g(-1), by 16% (P<0.01), and urine flow, absolute and fractional sodium excretions, by between 50-83% (all P<0.05). Renal nerves stimulation (0.7-1.3 Hz, 15V, 0.2 ms) decreased (P<0.02) left renal blood flow by 10% but had no effect on excretory variables, irrespective of nitrendipine administration. These results show that in renal failure rats the vascular and tubular responses to nitrendipine are preserved. However, the neural regulation of tubular reabsorption is abolished in this experimental model, irrespective of nitrendipine administration.     

Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate (Ap4A) and nicotinamide adenine dinucleotide (NAD) in rat.

Effects of Ap4A and NAD--precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus--1 micromol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparison with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pretreatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, whereas Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus--12 mg/kg followed by 1.2 mg/min/kg) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product--adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.     

Renal actions of atrial natriuretic peptide on the postischemic kidney

The objective of this study was to evaluate the renal actions of atrial natriuretic peptide (ANP) in the unilateral postischemic kidney of anesthetized dogs with a severe reduction in glomerular filtration rate. The dose of atrial natriuretic peptide (50 ng.kg-1.min-1) we gave did not alter the mean systemic arterial pressure, renal blood flow, and glomerular filtration rate in the normal kidney, as determined in foregoing studies. ANP was infused into the intrarenal artery continuously for 60 min after the release from 45 min of complete renal artery occlusion. In the vehicle-infused group, the glomerular filtration rate fell dramatically (6% of control), the renal blood flow decreased (60% of control), and the mean systemic arterial pressure tended to increase (136% of control). The urine flow rate and urinary excretion of sodium decreased significantly (25 and 25%, respectively) at 30 min after reflow in the postischemic period. Continuous renal artery infusion of ANP resulted in a marked increase in urine flow rate (246% of control) and the urinary excretion of sodium (286% of control). The administration of ANP led to an improvement in renal blood flow (99% of control) and glomerular filtration rate (40% of control), and attenuated the rise in mean systemic arterial pressure (109% of control), compared with findings in the vehicle-infused group. Plasma renin activity and prostaglandin E2 concentration in the renal venous blood were elevated after the release from complete renal artery occlusion in both groups. These results indicate that the vascular effects of ANP on the postischemic kidney were enhanced and that the peptide maintained the natriuretic effect.     

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.     

Influence of renal denervation on renal effects of acute nitric oxide and ETA/ETB receptor inhibition in conscious normotensive rats.

The role of renal nerves in the effects of concomitant NO synthase and non-selective ET(A/)ET(B) receptor inhibition on renal function was investigated in conscious normotensive Wistar rats. NO synthase inhibition alone (10 mg/kg b. w. i.v. L-NAME) in sham-operated rats with intact renal nerves induced an increase in systolic, diastolic and mean arterial pressure, urine flow rate, sodium, chloride and calcium excretion (p<0.05). The effect of L-NAME was markedly reduced by bosentan (10 mg/kg b.w. i.v.) and the values of urine flow rate, sodium, chloride and calcium excretions returned to control level (p<0.05). L-NAME administration one week after a bilateral renal denervation increased blood pressure to a similar extent as in sham-operated rats but decreased urine flow rate (p<0.05) and did not change electrolyte excretion. ET(A/)ET(B) receptor inhibition with bosentan during NO synthase inhibition in the renal denervated rats did not produce changes in urine flow rate or electrolyte excretion. NO synthase inhibition as well as concurrent NO synthase and ET(A/)ET(B) receptor inhibition did not change clearance of inulin or paraaminohippuric acid in sham-operated or renal denervated rats. These results indicate that renal sympathetic nerves play an important modulatory role in NO and endothelin induced effects on renal excretory function.     

Dietary sodium,glomerular filtration rate autoregulation,and glomerular size distribution profiles in domestic fowl (Gallus gallus)

Summary Mammalian glomerular filtration rate (GFR) autoregulation can be impaired by protocols that inhibit tubuloglomrular feedback, such as high sodium intake. Domestic fowl were fed diets containing either high sodium (0.39% Na: High-Na Group) or low sodium (0.03% Na: Low-Na Group). An arterial snare was used to reduce renal arterial perfusion pressure (RAPP) in a stepwise fashion to evaluate GFR autoregulation. Absolute sodium excretion, fractional sodium excretion (FE_Na), and ambient systemic arterial blood pressure were significantly elevated in the High-Na Group when compared with the Low-Na Group, and pressure natriuresis was abolished by the Low-Na diet. However, GFR autoregulatory profiles were identical in birds fed High-Na and Low-Na diets, suggesting that tubuloglomerular feed-back does not contribute significantly to avian GFR autoregulation. Filtering glomeruli were stained in vivo with alcian blue dye to determine if RAPP-induced reductions in GFR are associated with cessation of filtration (glomerular intermittency) by a portion of the nephron population. RAPP was held below the GFR autoregulatory range (experimental group) or was at ambient systemic arterial pressure (control group) during glomerular staining. Reducing RAPP below the autoregulatory range reduced GFR by 50%, but similar glomerular size distribution profiles were observed for experimental and control groups. These results indicate that sustained glomerular intermittency does not contribute to the decrease in GFR when RAPP is reduced below the autoregulatory range.Abbreviations BW body weight - C control - E excretion - FE fractional excretion - FF filtration fraction - GFR glomerular filtration rate - PAH p-amino hippuric acid - RAPP renal arterial perfusion pressure - RPF renal plasma flow - RT reptilian-type - SNGFR single nephron glomerular filtration rate - U _OSM urine osmolarity - UFR urine flow rate     

Central mu opioids mediate differential control of urine flow rate and urinary sodium excretion in conscious rats

Central administration of the selective mu opioid agonist, dermorphin, produces a concurrent diuretic and antinatriuretic response in conscious rats. To determine whether central mu opioids differentially affect the renal excretion of water and sodium, we examined changes in renal function produced by intracerebroventricular (i.c.v.) administration of dermorphin during continuous intravenous (i.v.) infusion of a synthetic ADH analogue in conscious Sprague-Dawley rats. During ADH infusion the typical diuresis produced by i.c.v. dermorphin was abolished although the antinatriuresis remained intact. Alone, I.v. ADH produced a decrease in urine flow rate without significantly altering urinary sodium excretion. In other studies, the effects of i.c.v. dermorphin were examined on the renal responses produced by i.v. infusion of a V₂-ADH receptor antagonist. In these studies the magnitude of the V₂ antagonist-induced diuresis was not altered by i.c.v. dermorphin but the increase in urinary sodium excretion produced by this antagonist was converted to an antinatriuresis. Central dermorphin did not alter heart rate or mean arterial pressure in either study. These findings suggest that the effects of central dermorphin on renal sodium and water handling are mediated by separate mechanisms; the effects on water involving changes in circulating ADH levels and the effects on sodium independent of the action of this hormone.     

Volume expansion during NOS substrate donation with L-arginine: regulatory offsetting of renal response?

The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg.kg(-1).min(-1)) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 +/- 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 +/- 0.0 to 0.7 +/- 0.1 ml/min). Volume expansion increased arterial blood pressure (102 +/- 3 to 114 +/- 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 +/- 31 micromol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 +/- 1.7 to 1.6 +/- 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 +/- 23 micromol/min at plasma ANG II levels of 3.0 +/- 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.     

Adenosine A(2A) receptors mediate cardiovascular responses to hypoxia in fetal sheep

Nonselective adenosine (ADO) receptor antagonists block hypoxia-induced bradycardia and hypertension in fetal sheep. This study was designed to determine the ADO receptor subtype that is involved in these cardiovascular responses. In chronically catheterized fetal sheep (>0.8 term), fetal hypoxemia was induced by having the ewe breathe a hypoxic gas mixture (9% O(2)-3% CO(2)-88% N(2)) for 1 h. Intra-arterial infusion of ZM-241385, an antagonist highly selective for ADO A(2A) receptors, to eight fetuses during normoxia significantly increased mean arterial pressure (MAP) from 42.5 +/- 2.0 to 46.1 +/- 2.0 mmHg without altering heart rate (HR). Infusion of a selective antagonist of ADO A(1) receptors [1, 3-dipropyl-8-cyclopentylxanthine (DPCPX)] elevated MAP and HR only after the infusion was terminated, although administration of the vehicle for ZM-241385 or DPCPX had no effect on MAP or HR. Isocapnic hypoxia with infusion of DPCPX or the vehicle for DPCPX or ZM-241385 produced a transient fall in HR, a rise in MAP, and a decrease in plasma volume. In contrast, ADO A(2A) receptor blockade abolished the hypoxia-induced bradycardia and hypertension and blunted the decline in plasma volume. We conclude that fetal ADO A(2A) receptors: 1) modulate AP during normoxia, and 2) mediate cardiovascular responses during acute O(2) deficiency.     

Chronic hydralazine treatment alters the acute pressure-natriuresis curve in young spontaneously hypertensive rats

The pressure-natriuresis relationship was studied in anesthetized, 7- to 9-week-old control spontaneously hypertensive rats (SHR) and in SHR that had been treated with hydralazine (20 mg.kg-1.day-1 in drinking water) starting at 4-5 weeks of age. To minimize reflex changes in kidney function during changes in renal artery pressure, neural and hormonal influences on the kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a hormone cocktail (330 microL.kg-1.mikn-1) containing high levels of aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved in 0.9% NaCl containing 1% albumin. Changes in renal function were measured using standard clearance techniques, while renal artery pressure was varied between 136 +/- 1 and 186 +/- 2 mmHg (1 mmHg = 133.32 Pa) in control SHR (n = 10) and between 113 +/- 1 and 162 +/- 2 mmHg in treated SHR (n = 11). Mean arterial pressure (+/- SE) under Inactin anesthesia was 172 +/- 3 mmHg in control SHR and 146 +/- 3 mmHg in treated SHR (p less than 0.05). Where renal artery pressure overlapped between groups, there were no significant differences in glomerular filtration rate. Renal blood flow was also similar in both groups, although at 160 mmHg blood flow was slightly but significantly reduced in treated SHR. Urine flow and total and fractional sodium excretion increased similarly with increases in renal artery pressure in both groups, but the pressure-natriuresis curve in hydralazine-treated SHR was displaced to the left along the pressure axis. The data indicate that chronic administration of hydralazine in young SHR enhances fractional sodium excretion, suggesting that tubular reabsorption of sodium is decreased by hydralazine.     

Effect of angiotensin converting enzyme inhibition on renal response to atrial natriuretic factor in rats

Previous studies have shown that atrial natriuretic factor (ANF) inhibits renin secretion whereas cilazapril blocks angiotensin II generation via converting enzyme inhibition. Both agents enhance renal excretory function. The present study was conducted to test whether the renin-angiotension system is involved in the ANF-induced renal effects. ANF was administered to anesthetized normal rats (n = 16) with or without a simultaneous infusion of cilazapril. Single bolus injections of ANF at doses of 2.5 micrograms/kg and 5.0 micrograms/kg significantly decreased mean arterial blood pressure by 6.8 +/- 2.3% and 9.4 +/- 2.2%, respectively. The corresponding increases in glomerular filtration rate were 5.6 +/- 3.7% and 8.4 +/- 2.8%, in absolute sodium excretion were 55.0 +/- 18.5% and 105.2 +/- 39.9%, and in urine flow were 24.8 +/- 9.3% and 35.6 +/- 14.6%. Intravenous infusion of cilazapril (33 micrograms/kg.min) reduced the arterial blood pressure, elevated the glomerular filtration rate and increased sodium and water excretion. The corresponding doses of ANF administration during continuous infusion of cilazapril further decreased blood pressure by 8.3 +/- 1.9% and 10.9 +/- 5.4%, respectively. However, there were no significant changes in the glomerular filtration rate and sodium and water excretion. The failure of ANF to exhibit a renal effect was irrelevant to the lowering blood pressure induced by cilazapril. These results suggest that reduced endogenous angiotensin II generation contributes to the renal, but not the hypotensive, effect of ANF.     

A role for the angiotensin IV/AT4 system in mediating natriuresis in the rat

Angiotensin II (AngII) or Angiotensin IV (AngIV) was infused into the renal artery of anesthetized rats while renal cortical blood flow was measured via laser Doppler flowmetry. The infusion of AngII produced a significant elevation in mean arterial pressure (MAP) with an accompanying decrease in cortical blood flow, glomerular filtration rate (GFR), urine volume, and urine sodium excretion. The infusion of AngIV induced significant increases in renal cortical blood flow and urine sodium excretion, without altering MAP, GFR, and urine volume. Pretreatment infusion with a specific AT1 receptor antagonist, DuP 753, blocked or attenuated the subsequent AngII effects, while pretreatment infusion with the specific AT4 receptor antagonist, Divalinal-AngIV, blocked the AngIV effects. These results support distinct and opposite roles for AngII and AngIV, i.e. AngII acts as an anti-natriuretic agent, while AngIV acts as a natriuretic agent.     

肾动脉内注射腺苷兴奋肾神经传入纤维的自发活动

应用记录肾神经传入纤维多单位和单位放电的方法,观察肾动脉内注射腺苷对麻醉家兔肾神经传入纤维自发放电活动的影响。结果表明：(1)肾动脉内注射50,100和200nmol／kg腺苷可呈剂量依赖性地兴奋肾神经传入纤维的活动,而动脉血压不变。(2)肾动脉内预先应用选择性腺苷A1受体阻断剂DPCPX(160nmol/kg),可部分阻断腺苷对肾神经传入纤维的兴奋作用。(3)静脉应用一氧化氮合酶抑制剂L-NAME(0．1mmol／kg)预处理,延长并增强了肾神经传入纤维对腺苷的反应。以上结果提示,肾动脉内应用腺苷可兴奋肾传入纤维的自发放电活动,一氧化氮作为抑制性因素参与腺苷诱导的肾神经传入纤维兴奋。     

State-dependent expression of pressure diuresis in conscious rats

In 1967, Guyton and Coleman modeled pressure diuresis as the underlying, essential, long-term mechanism that regulates arterial pressure when sodium intake changes. Other mechanisms that influence renal function interact with pressure diuresis to achieve sodium balance and determine the blood pressure. Increases in sodium intake suppress sodium conserving mechanisms and activate natriuretic mechanisms; decreases in sodium intake have the opposite effect. If the Guyton-Coleman model is correct, then pressure diuresis should be more readily detected in animals on a high-salt diet than in animals on a low-salt diet. We measured spontaneous changes in arterial pressure and urine flow in conscious rats fed low-salt (0. 4% NaCl) and high-salt (8.0% NaCl) chow. For 10 rats fed a high-salt diet, arterial pressure and urine flow were positively correlated in 19 of 32 (59%) trials. In 10 rats fed a low-salt diet, a positive correlation was observed in 10 of 33 (30%) trials. Chi-square analysis revealed that differences in Na+ content of the diet were significantly associated with the probability of a positive relationship between blood pressure and urine flow. These results support the hypothesis that the expression of pressure diuresis across time is dependent on the state of sodium balance.     

Role of the paraventricular nucleus in renal excretory responses to acute volume expansion: role of nitric oxide

Acute volume expansion (VE) produces a suppression of renal sympathetic nerve discharge (RSND) resulting in diuresis and natriuresis. Recently, we have demonstrated that the endogenous nitric oxide (NO) system within the paraventricular nucleus (PVN) produces a decrease in RSND. We hypothesized that endogenous NO in the PVN is involved in the suppression of RSND leading to diuretic and natriuretic responses to acute VE. To test this hypothesis, we first measured the VE-induced increase in renal sodium excretion and urine flow with and without blockade of NO, with microinjection of NG-monomethyl-L-arginine (L-NMMA; 200 pmol in 200 nl), within the PVN of Inactin-anesthetized male Sprague-Dawley rats. Acute VE produced significant increases in urine flow and sodium excretion, which were diminished in rats treated with L-NMMA within the PVN. This effect of NO blockade within the PVN on VE-induced diuresis and natriuresis was abolished by renal denervation. Consistent with these data, acute VE induced a decrease in RSND (52% of the baseline level), which was significantly blunted by prior administration of L-NMMA into the PVN (28% of the baseline level) induced by a comparable level of acute VE. Using the push-pull perfusion technique, we found that acute VE induced a significant increase in NOx concentration in the perfusate from the PVN region. Taken together, these results suggest that acute VE induces an increase in NO production within the PVN that leads to renal sympathoinhibition, resulting in diuresis and natriuresis. We conclude that NO within the PVN plays an important role in regulation of sodium and water excretions in the volume reflex via modulating renal sympathetic outflow.     

Interaction among atrial natriuretic factor (ANF), vasopressin, and renal nerves in terms of renal responses in rats.

The relationship between the renal nerves and vasopressin in terms of the natriuretic and diuretic responses to atrial natriuretic factor (ANF--0.25 microgram/kg/min for 15 min), was investigated in unilaterally denervated anesthetized rats before and after the administration of a vasopressin V2 specific antagonist (AVPX)--(40 micrograms/kg bolus followed by 0.4 microgram/kg/min infusion). Administration of the AVPX or ANF did not alter the arterial pressure. Acute renal denervation or AVPX administration independently produced significant increases in sodium and water excretion. ANF infusion by itself produced a greater increase in urine flow and sodium excretion from the denervated kidney compared to the intact kidney before the administration of AVPX. However, after the administration of AVPX renal responses to ANF from the intact kidneys were enhanced such that they were not significantly different from the denervated kidneys. These results suggest that the full physiological response to ANF may be masked by tonic renal nerve activity or antidiuretic actions of vasopressin. Furthermore, since combined renal denervation and AVPX administration does not produce any greater potentiation of the renal responses to ANF than either of these manipulations alone, it is suggested that they may act via a common mechanism, possibly altering activity in the renal nerves.