Role of intrarenal alpha(2)-adrenoceptors in the renal responses to xylazine in rats

This study examined the contribution of intrarenal alpha(2)-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (U(Na)V) responses in ketamine-xylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the alpha(2)-adrenoceptor antagonist yohimbine (5 microg) significantly decreased V from 58 +/- 8 to 35 +/- 7 microl. min(-1). g kidney wt(-1) and U(Na)V from 2.8 +/- 0.4 to 2.1 +/- 0.4 microeq. min(-1). g kidney wt(-1) without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bilaterally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yohimbine (15 microg) significantly reduced left and right kidney V, with no effects on U(Na)V. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg), 20 min after intravenous injection, significantly decreased V from 63 +/- 9 to 13 +/- 2 microl. min(-1). g kidney wt(-1 )and U(Na)V from 4.5 +/- 0.5 to 1.1 +/- 0.1 microeq. min(-1). g kidney wt(-1). In RDNX rats, this dose of yohimbine reduced V and U(Na)V, but the magnitude was blunted compared with intact rats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and U(Na)V to similar magnitudes in intact and RDNX groups. Together, these findings indicate that intravenous xylazine acts by renal nerve-dependent and -independent mechanisms to enhance renal excretory function in ketamine-anesthetized rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal action to augment the renal excretion of water and sodium via a presynaptic alpha(2)-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.     

Acute and chronic increases in osmolality increase excitatory amino acid drive of the rostral ventrolateral medulla in rats

Water deprivation is associated with increased excitatory amino acid (EAA) drive of the rostral ventrolateral medulla (RVLM), but the mechanism is unknown. This study tested the hypotheses that the increased EAA activity is mediated by decreased blood volume and/or increased osmolality. This was first tested in urethane-anesthetized rats by determining whether bilateral microinjection of kynurenate (KYN, 2.7 nmol) into the RVLM decreases arterial pressure less in water-deprived rats after normalization of blood volume by intravenous infusion of isotonic saline or after normalization of plasma osmolality by intravenous infusion of 5% dextrose in water (5DW). Water-deprived rats exhibited decreased plasma volume and elevated plasma osmolality, hematocrit, and plasma sodium, chloride, and protein levels (all P < 0.05). KYN microinjection decreased arterial pressure by 24 +/- 2 mmHg (P < 0.05; n = 17). The depressor response was not altered following isotonic saline infusion but, while still present (P < 0.05), was reduced (P < 0.05) to -13 +/- 2 mmHg soon after 5DW infusion. These data suggest that the high osmolality, but not low blood volume, contributes to the KYN depressor response. To further investigate the action of increased osmolality on EAA input to RVLM, water-replete rats were also studied after hypertonic saline infusion. Whereas KYN microinjection did not decrease pressure immediately following the infusion, a depressor response gradually developed over the next 3 h. Lumbar sympathetic nerve activity also gradually increased to up to 167 +/- 19% of control (P < 0.05) 3 h after hypertonic saline infusion. In conclusion, acute and chronic increases in osmolality appear to increase EAA drive of the RVLM.     

延髓腹外侧区微量注射L－NNA和SNP对大鼠血压、心率和肾交感神经活动的影响

在麻醉大鼠观察了向延髓腹外侧区微量注射ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（ＬＮＮＡ）和硝普钢（ＳＮＰ）对血压、心率和肾交感神经活动的影响,旨在探讨中枢左旋精氨酸－ＮＯ通路在动脉血压调节中的作用及其机制。实验结果如下：（１）向延髓腹外侧头端区（ＲＶＬＭ）注射Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,肾交感神经活动（ＲＳＮＡ）增强;心率（ＨＲ）减慢,但无统计学意义。ＭＡＰ和ＲＳＮＡ的变化持续３０ｍｉｎ以上;此效应可被预先静注左旋精氨酸所逆转。（２）向ＲＶＬＭ微量注射ＳＮＰ,ＭＡＰ降低,ＲＳＮＡ减弱;但ＨＲ的变化无统计学意义。（３）向延髓腹外侧尾端区（ＣＶＬＭ）注射Ｌ－ＮＮＡ,ＭＡＰ降低,ＨＲ减慢,ＲＳＮＡ减弱。（４）向ＣＶＬＭ微量注射ＳＮＰ,ＭＡＰ升高,ＲＳＮＡ增强,而心率无明显变化。以上结果表明,中枢左旋精氨酸－ＮＯ通路对延髓腹外侧部的神经元活动有调变作用。     

Activation of histamine H3 receptors inhibits renal noradrenergic neurotransmission in anesthetized dogs

To investigate the possible involvement of histamine H(3) receptors in renal noradrenergic neurotransmission, effects of (R)alpha-methylhistamine (R-HA), a selective H3-receptor agonist, and thioperamide (Thiop), a selective H3-receptor antagonist, on renal nerve stimulation (RNS)-induced changes in renal function and norepinephrine (NE) overflow in anesthetized dogs were examined. RNS (0.5-2.0 Hz) produced significant decreases in urine flow and urinary sodium excretion and increases in NE overflow rate (NEOR), without affecting renal hemodynamics. When R-HA (1 microg x kg(-1) x min(-1)) was infused intravenously, mean arterial pressure and heart rate were significantly decreased, and there was a tendency to reduce basal values of urine flow and urinary sodium excretion. During R-HA infusion, RNS-induced antidiuretic action and increases in NEOR were markedly attenuated. Thiop infusion (5 microg x kg(-1) x min(-1)) did not affect basal hemodynamic and excretory parameters. Thiop infusion caused RNS-induced antidiuretic action and increases in NEOR similar to the basal condition. When R-HA was administered concomitantly with Thiop infusion, R-HA failed to attenuate the RNS-induced antidiuretic action and increases in NEOR. However, in the presence of pyrilamine (a selective H1-receptor antagonist) or cimetidine (a selective H2-receptor antagonist) infusion, R-HA attenuated the RNS-induced actions, similarly to the case without these antagonists. Thus functional histamine H3 receptors, possibly located on renal noradrenergic nerve endings, may play the role of inhibitory modulators of renal noradrenergic neurotransmission.     

Abnormal response of urinary eicosanoid system to norepinephrine infusion in patients with essential hypertension.

To define the role of the renal eicosanoid system in sustaining renal homeostasis in hypertension, we investigated the alterations in urinary excretions of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of vasodepressor prostacyclin, and thromboxane B2 (TXB2), a stable metabolite of vasoconstrictor TXA2, when norepinephrine was continuously infused for 90 min in hypertensive (n = 13) and normotensive subjects (n = 14). There was no difference in plasma norepinephrine concentration after the infusion between the hypertensive and the normotensive subjects. Moreover, the percent changes in renal vascular resistance elicited by norepinephrine in the hypertensives were equal to those of the normotensive subjects. In the normotensive subjects, the norepinephrine infusion significantly increased urinary 6-keto-PGF1 alpha excretion and decreased urinary excretion of TX, both of which are beneficial for sustaining renal function. In fact, the greater the production of renal 6-keto-PGF1 alpha was, the less the reduction of renal blood flow and urinary sodium excretion was. In the hypertensive subjects, however, these normal responses of the renal eicosanoid system, seen in the normotensives, were abolished; urinary 6-keto-PGF1 alpha was unaltered and thromboxane generation was rather increased. Thus, the renal eicosanoid system dysfunctions in hypertensive subjects when the renal circulation is challenged by norepinephrine. These abnormal responses are likely to cause sodium retention and could contribute, in part, to the hypertensive mechanism in patients with essential hypertension.     

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.     

The effect of sodium intake on renal prostaglandin production

The effect of chronic alterations in dietary sodium intake on renal arachidonic acid (AA) metabolism was studied in male Wistar rats who were maintained for 14 days on a diet consisting of sodium-deficient food and either deionized water (low salt intake, LSI), 1% saline (normal salt intake, NSI), or 2% saline (high salt intake, HSI). 24 h Urinary Sodium (UNaV) and plasma renin activity (PRA) measurements were shown to validate the dietary protocol. Microsomal preparations from the cortices and medullae were incubated with radiolabeled exogenous AA, and endogenous urinary prostaglandin (PG) levels were assayed by RIA to quantify renal PG synthesis. Cortical PGF2 alpha and PGE2 synthesis was found to be the greatest following LSI. In contrast, medullary PGF2 alpha was shown to be the least following LSI and to increase with increased sodium intake. Likewise, urinary PGF2 alpha levels significantly increased with increasing sodium intake. Changes in urinary PGE2 levels showed the same trend as PGF2 alpha but did not achieve statistical significance. These data show that dietary sodium differentially affects renal cortical and medullary PG synthesis and may reflect physiological differences in the regulation of cyclooxygenase in these zones. These data further suggest that the major source of urinary PGs is the renal medulla since the relationship of urinary levels to sodium intake mimics that described for the synthesis of PGs by the medullary tissue.     

Renal mechanisms involved in stress-induced antinatriuresis and antidiuresis in rats

The present study was conducted to investigate if changes in sodium and water excretion in stressed animals were due to modifications in the glomerular filtration rate (GFR) and to determine the participation of angiotensin II (Ang II) and alpha and beta-adrenoceptors on sodium and water renal excretion in rats subjected to immobilization stress (IMO). Male Wistar rats (250-300 g) were randomly separated into five different groups and vehicle (0.9% NaCl) via intraperitoneal (i.p.) or propanolol (3 mg/kg i.p.) or captopril (6 mg/kg i.p.) or yohimbine (3 mg/kg i.p.) or prazosin (1 mg/kg i.p.) were injected respectively. During experimental measurements, the animals were kept in metabolic cages for 6 h and sodium, potassium and water renal excretion and saline (1.5% NaCl) and water intake were determined at day 1 (drug effect) and day 7 (drug + IMO effects). GFR was measured by creatinine clearance in control and IMO rats. A stress-induced antinatriuresis and antidiuresis was reversed by alpha 1 and alpha 2-adrenoceptor antagonists, while captopril inhibited only the antidiuresis and propranolol had no effect on either parameter. No differences were observed in creatinine clearance in the studied groups. Since yohimbine blocks alpha 2-adrenoceptors and prazosin blocks alpha 1-adrenoceptors and alpha 2B-adrenoceptors, the stress-induced renal sodium reabsorption mainly could be attributed to alpha 2B-adrenoceptors. The present results indicate that beta-adrenoceptors do not participate in this response and, Ang II only reverses the antidiuresis and shows a slight participation in antinatriuresis. The increment in sodium and water reabsorption caused by IMO occurred without changes in the glomerular filtration rate.     

Ca2+ antagonists and db-cAMP sustain a rise in renal blood flow induced by acetylcholine in indomethacin-treated dogs

Renal arterial infusion of acetylcholine (ACh) in the dog normally produces a sustained rise in sodium excretion (UNaV) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis is inhibited, ACh induces only a transient increase in UNaV and RPF followed by a progressive decline in UNaV and RPF, and a rise in renin secretory rate (RSR). Renal arterial infusion of PGE2 but not a vasodilator such as bradykinin restored the response to ACh to normal in indomethacin (Indo)-treated dogs. During renal arterial infusion of dibutyryl cyclic AMP (6 mg/min), ACh also produced a sustained increase in UNaV and RPF despite an inhibition of PG synthesis by Indo. Renal arterial infusion of verapamil (60 micrograms/min) or diltiazem (60 micrograms/min) also prevented the subsequent fall in RPF when ACh was infused; RSR, however, did not show a rise. The results suggest that synthesis of PGE2 with stimulation of cAMP is required for sustained ACh action. When PGE synthesis is inhibited, ACh may produce renal vasoconstriction by increasing intracellular Ca2+ concentration. The partial effect of calcium channel blockers suggests that release of calcium from intracellular stores as well as calcium entry may mediate the response.     

Chronic administration of adrenomedullin attenuates the hypertension and increases renal nitric oxide synthase in Dahl salt-sensitive rats

Adrenomedullin reduces systemic blood pressure and increases urinary sodium excretion partly through the release of nitric oxide. We hypothesized that chronic adrenomedullin infusion ameliorates salt-sensitive hypertension and increases the expression of renal nitric oxide synthase (NOS) in Dahl salt-sensitive (DS) rats, because the reduced renal NOS expression promotes salt sensitivity. DS rats and Dahl salt-resistant (DR) rats were fed a high sodium diet (8.0% NaCl) for 3 weeks. The high sodium diet resulted in an increase in blood pressure and a reduction of urinary sodium excretion in association with increased renal adrenomedullin concentrations and decreased expression of renal neuronal NOS (nNOS) and renal medullary endothelial NOS (eNOS) in DS rats compared with DR rats. Chronic adrenomedullin infusion partly inhibited the increase of blood pressure and proteinuria in association with a restoration of renal nNOS and medullary eNOS expression in DS rats under the high sodium diet. The immunohistochemical analysis revealed that the restored renal nNOS expression induced by chronic adrenomedullin infusion may reflect the restoration of nNOS expression in the macula densa and inner medullary collecting duct. These results suggest that adrenomedullin infusion has beneficial effects on this hypertension probably in part through restored renal NOS expression in DS rats.     

Sympathoinhibition from ventrolateral periaqueductal gray mediated by 5-HT(1A) receptors in the RVLM

The role of 5-hydroxytryptamine 1A (5-HT(1A)) receptors located in the rostral ventrolateral medulla (RVLM) in the mediation of a sympathoinhibitory and depressor response elicited from the ventrolateral periaqueductal gray (vlPAG) matter of the midbrain was examined in pentobarbital sodium-anesthetized rats. Activation of neurons in the vlPAG evoked a decrease in renal and lumbar sympathetic nerve activities and a decrease in arterial blood pressure. After microinjection of the specific 5-HT(1A)-receptor antagonist WAY-100635 into the pressor area of the RVLM, the vlPAG-evoked sympathoinhibition and hypotension was attenuated to control levels (7 of 15 animals) or converted into a sympathoexcitation and pressor response (8 of 15 animals). Baroreflex inhibition of sympathetic nerve activity was not impaired by microinjection of WAY into the sympathoexcitatory region of the RVLM. These data suggest that sympathoinhibition and hypotension elicited by activation of neurons in the vlPAG are mediated by 5-HT(1A) receptors in the RVLM.     

Role of transmitters in mediating hypothalamic control of electrolyte excretion.

Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway.     

Oxidative stress alters renal D1 and AT1 receptor functions and increases blood pressure in old rats

Aging is associated with an increase in oxidative stress and blood pressure (BP). Renal dopamine D1 (D1R) and angiotensin II AT1 (AT1R) receptors maintain sodium homeostasis and BP. We hypothesized that age-associated increase in oxidative stress causes altered D1R and AT1R functions and high BP in aging. To test this, adult (3 mo) and old (21 mo) Fischer 344 × Brown Norway F1 rats were supplemented without/with antioxidant tempol followed by determining oxidative stress markers (urinary antioxidant capacity, proximal tubular NADPH-gp91phox, and plasma 8-isoprostane), D1R and AT1R functions, and BP. The D1R and AT1R functions were determined by measuring diuretic and natriuretic responses to D1R agonist (SKF-38393; 1 μg·kg(-1)·min(-1) iv) and AT1R antagonist (candesartan; 10 μg/kg iv), respectively. We found that the total urinary antioxidant capacity was lower in old rats, which increased with tempol treatment. In addition, tempol decreased the elevated NADPH-gp91phox and 8-isoprostane levels in old rats. Systolic, diastolic, and mean arterial BPs were higher in old rats and were reduced by tempol. Although SKF-38393 produced diuresis in both adult and old rats, urinary sodium excretion (UNaV) increased only in adult rats. While candesartan increased diuresis and UNaV in adult and old rats, the magnitude of response was greater in old rats. Tempol treatment in old rats reduced candesartan-induced increase in diuresis and UNaV. Our results demonstrate that diminished renal D1R and exaggerated AT1R functions are associated with high BP in old rats. Furthermore, oxidative stress may cause altered renal D1R and AT1R functions and high BP in old rats.     

Human parathyroid hormone (1-34) increases urinary excretion of lysosomal enzymes in rats

The kidney is the major target of parathyroid hormone (PTH), and PTH influences the urinary excretion of calcium, phosphate and hydrogen ions. It was previously reported that the urinary, excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases after human PTH (hPTH) (1-34) infusion in normal subjects and idiopathic hypoparathyroidism patients, but not in pseudohypoparathyroidism type I patients. Here we report that intravenous infusion of hPTH(1-34) to rats transiently increased the urinary excretion of various lysosomal enzymes, such as beta-glucuronidase and acid phosphatase as well as NAG. However, it did not affect the urinary excretion of tubular brush border membrane enzymes, i.e. alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase. Human PTH(1-34) dose-dependently increased the urinary excretion of NAG in rats with a peak at 30 min, which returned to a baseline within 60 min. The increase in the urinary NAG excretion caused by hPTH(1-34) positively correlated with the increase in the urinary cAMP excretion (r = 0.844, p < 0.01), and infusion of dibutyryl cAMP at a dose of 20 mg/kg similarly increased the urinary excretion of NAG. These results suggested that the increase in the urinary excretion of lysosomal enzymes caused by hPTH(1-34) may be a functional response to hPTH(1-34) occurring in the renal tubules via PTH signaling pathway.     

The effects of vasopressin on renal sodium excretion in pigs given intravascular hypertonic salt loads

Young pigs of about 25-30 kg liveweight were given intravenous infusions of a hypertonic sodium chloride solution (4-6 mol.1(-1)) at rates varying from 2-6 mmol.min-1. Such infusions resulted in a marked increase in the urine flow and in urinary sodium excretion, the size of these increases being proportional to infusion rate. Circulating vasopressin levels were also markedly increased, the size of these increases being the same as those seen in other pigs given exogenous vasopressin in amounts which were shown to increase urinary sodium excretion. This suggests that vasopressin was probably contributing to the increase in renal sodium excretion seen in those pigs given the intravenous salt loads.     

脑室内注射高张盐水抑制近曲小管对水和钠的重吸收

实验在麻醉大鼠上进行。用锂清除率为指标观察脑室内注射高张盐水对近曲小管重吸收水和钠的影响。在切断单侧肾神经的动物中,脑室内注射高张盐水后的锂清除率与肾小球滤过率比值在去神经侧肾脏从0.37±0.04增加至0.51±0.05(P<0.01);神经完好侧肾脏则从0.26±0.03增加至0.31±0.04(P<0.05);双侧肾脏的肾小球滤过率、尿量、尿钠和尿钾量均增加,且去肾神经肾脏的增加幅度高于肾神经完好肾脏。在肾小管微穿刺实验中,脑室内注射高张盐水后,近曲小管末段小管液流量从24.42±1.84nl/min增加至31.86±3.09nl/min(P<0.01),小管液的渗透压无显著变化。以上实验结果表明,脑室内注射高张盐水引起的利尿、尿钠增多反应与肾小球滤过率增加和近曲小管对水、钠重吸收减少有关,体液因素在该反应中可能起主要作用。     

Effects of captopril and enalapril on sodium excretion and blood pressure in sodium-deficient dogs

Inhibition of angiotensin I-converting enzyme (ACE) (kininase II) provides a powerful new method for evaluating the role of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the control of aldosterone secretion, renal function, and arterial blood pressure. This study compares the effects of long-term administration of a sulfhydryl inhibitor, captopril, with a nonsulfhydryl inhibitor, enalapril (1-[N-[1-(ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-L-proline), in conscious sodium-deficient dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), urinary sodium excretion (UNaV), arterial pressure (AP), blood kinins (BK), urinary kinins (UK), and urinary kallikrein activity (UKA) were determined during long-term inhibition of ACE in sodium-deficient dogs. In response to captopril administration (20 mg/(kg . day], PAC decreased from 38.9 +/- 6.7 to 14.3 +/- 2.3 ng/dl, PRA increased from 3.58 +/- 0.53 to 13.7 +/- 1.6 ng/(ml . h), UNaV increased from 0.65 +/- 0.27 to 6.4 +/- 1.2 meq/day, AP decreased from 102 +/- 3 to 65 +/- 2 mm Hg, BK increased from 0.17 +/- 0.02 to 0.41 +/- 0.04 ng/ml, UK increased from 7.2 +/- 1.5 to 31.4 +/- 3.2 micrograms/day, and UKA decreased from 23.6 +/- 3.1 to 5.3 +/- 1.2 EU/day. Quantitatively similar changes in AP, UNaV, and PAC were observed in sodium-deficient dogs in response to long-term enalapril administration (4 mg/(kg X day]. In sodium-deficient dogs maintained on captopril or enalapril for several days, angiotensin II (AngII) infusion (3 ng/(kg X min] restored PAC, UNaV, and AP to levels observed in untreated sodium-deficient dogs. These data indicate that the long-term hypotensive and natriuretic actions of inhibitors of ACE are mediated by inhibition of AngII formation and that the renin-angiotensin system plays an essential role in regulating aldosterone secretion, renal function, and AP during sodium deficiency.     

Role of volume and prostaglandin synthesis in the suppression of renin by saline in the rat

To evaluate the contribution of plasma volume expansion per se on acute inhibition of renin release by sodium chloride infusion, renin responses to comparable plasma volume expansion with intravenous infusions of sodium chloride, sodium bicarbonate, or albumin were studied in separate groups of sodium chloride-depleted rats. In addition, urinary prostaglandin E2 (PGE2) excretion rate was compared in the saline- and sodium bicarbonate-infused animals to evaluate the relationship between acute changes in renin release and intrarenal PGE2 synthesis. All three groups were plasma volume-expanded by approximately 55%. Plasma renin activity (PRA) decreased in response to saline (12.3 +/- 1.0 to 6.7 +/- 0.7 ng AI/ml/hr; P less than 0.01) whereas PRA did not change with sodium bicarbonate (11.3 +/- 1.4 to 10.2 +/- 1.5) or albumin (9.9 +/- 0.7 to 8.2 +/- 1.0). The rate of PGE2 excretion was not changed by either saline (72.2 +/- 13.1 to 72.3 +/- 18.7 pg/min) or sodium bicarbonate infusion (70.7 +/- 8.8 to 64.9 +/- 7.0). These results support the hypothesis that acute suppression of PRA by infusion of saline is not dependent upon volume expansion per se. In confirmation of earlier observations, inhibition of renin release by sodium chloride was related to chloride. Finally, the results suggest that the renal tubular mechanism for inhibition of renin release by sodium chloride is not related to overall changes in renal PGE2 synthesis in the rat.     

Characterization of noradrenergic transmission at the dorsal motor nucleus of the vagus involved in reflex control of fundus tone

Quantitative analysis of innervation to dorsal motor nucleus of the vagus (DMV) fundus-projecting neurons indicates that approximately 17% of input neurons are noradrenergic. To determine whether this small percentage of neurons innervating DMV output to the stomach is physiologically relevant, we evaluated the role of norepinephrine at the DMV in mediating a vagovagal reflex controlling the fundus. A strain gauge was sutured onto the fundus of isoflurane-anesthetized rats to monitor changes in tone evoked by esophageal distension (ED). ED produced a decrease in fundus tone of 0.31 +/- 0.02 g (P < 0.05), which could be reproduced after a 30-min interval between distensions. Bilateral cervical vagotomy and/or pretreatment with intravenous atropine methylbromide prevented the reflex-induced fundus relaxation. In contrast, intravenous N(G)-nitro-L-arginine methyl ester had no effect. Bilateral microinjection of alpha2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Before microinjection of alpha2-adrenoreceptor antagonists, ED decreased fundus tone by 0.33 +/- 0.05 g (P < 0.05). After antagonist microinjection, ED decreased fundus tone by only 0.05 +/- 0.06 g (P > 0.05). Bilateral microinjection of prazosin into the DMV had no effect on the response. Microinjection of norepinephrine into the DMV mimicked the effect of ED and was also prevented by prior microinjection of an alpha2-adrenoreceptor antagonist. Our results indicate that noradrenergic innervation of DMV fundus-projecting neurons is physiologically important and suggest that norepinephrine released at the DMV acts on alpha2-adrenoreceptors to inhibit activity in a cholinergic-cholinergic excitatory pathway to the fundus.     

The effect of prostaglandin synthetase inhibitors on renal function: studies in normal rats during sodium or water diuresis and in rats with chronic renal insufficiency

The effect of acute infusion of the prostaglandin synthetase inhibitors - meclofenamate or indomethacin - was examined in awake rats. Studies were performed in normal rats undergoing either sodium or water diuresis and in salt-replete rats with chronic renal insufficiency. Prostaglandin synthetase inhibitors had no effect on renal plasma flow, glomerular filtration rate or fractional excretion of sodium in any of the groups. Absolute urinary excretion rates for sodium and potassium decreased only in the normal, salt-replete rats. In contrast, prostaglandin synthetase inhibitors consistently decreased urinary flow and osmolar clearance under all experimental conditions studied. In the normal, salt-replete rats the fall in urine flow was preceded by an increase in urinary excretion of cyclic AMP. These results show that inhibitors of prostaglandin synthesis enhance the ability of the kidney to reabsorb water. This effect may be secondary to increased cyclic AMP generation and to increased urea recirculation resulting in higher urea accumulation in the renal medulla.