Biomedical subjects

A D Baines

Publications and source records attributed to A D Baines.

At least 37 records · Page 2Linked to original sources

PubMed1990

Role of diacylglycerol in adrenergic-stimulated 86Rb uptake by proximal tubules.

We used rat proximal tubule fragments purified by Percoll centrifugation to examine the role of diacylglycerol (DAG) in noradrenergic-stimulated Na+ reabsorption. Tubular DAG concentration and ouabain-inhibitable 86Rb uptake increased within 30 s after adding norepinephrine (NE) and remained elevated for at least 5 min. NE (1 microM) increased DAG content 17% and ouabain-inhibitable 86Rb uptake 23%. Cirazoline-stimulated 86Rb uptake was not inhibited by BaCl, quinidine, or bumetanide (1-10 microM) or by the omission of HCO3- or Cl- from the medium, but it was completely inhibited by ouabain and furosemide. Oleoyl-acetyl glycerol, L-alpha-1,2-dioctanoylglycerol, and L-alpha-1,2-dioleoylglycerol (DOG) increased total 86Rb uptake 8-11%. 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 nM) increased uptake by only 4%. Staurosporine at 5 nM inhibited DOG stimulation completely, whereas 50 nM staurosporine was required to inhibit NE stimulation completely. Sphingosine inhibited DOG stimulation by 66% but did not inhibit NE stimulation. Amiloride (1 mM) completely blocked DOG stimulation. Monensin increased 86Rb uptake 31% and completely blocked the DOG effect but reduced the NE effect by only 26% (P = 0.08). In tubules from salt-loaded rats, NE did not increase DAG concentration, but NE-stimulated 86Rb uptake was reduced by only 23% (P = 0.15). Thus DAG released by NE may stimulate Na+ entry through Na(+)-H+ exchange. NE predominantly stimulates Na(+)-K(+)-adenosinetriphosphatase (ATPase) by activating a protein kinase that is insensitive to DAG and TPA and is inhibited by staurosporine but not by sphingosine. NE may also stimulate K+ efflux through a BaCl-insensitive K+ channel that is inhibited by millimolar furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

PubMed1990

Mechanisms of perfused kidney cytoprotection by alanine and glycine.

We examined the cytoprotective action of individual amino acids in isolated perfused kidneys during perfusion with either 10 mM lactate or 5 mM glucose. In the absence of amino acids inulin clearance fell rapidly, whereas fractional excretion of phosphate, lactate, or glucose increased to more than 30%; lactate dehydrogenase was released into perfusate and alkaline phosphatase into the urine. Functional deterioration was less in kidneys from rats rendered chronically water diuretic by drinking 5% glucose. Adding 5 mM glycine, L-alanine, beta-alanine, or D-alanine to the perfusate also prevented functional deterioration and release of enzymes. Glycine perfusion increased total phospholipid per microgram DNA by 6%. Aspartate, glutamate, glutamine, taurine, isoleucine, leucine, and valine were not protective. Serine, proline, and alpha-aminoisobutyric acid had small protective effects. Micropuncture measurements of proximal tubular free- and stop-flow pressures showed no effect of L-alanine on glomerular hemodynamics. L-Alanine increased oxygen consumption by both glucose- and lactate-perfused kidneys and increased gluconeogenesis by lactate-perfused kidneys but did not alter renal ATP content or energy charge. L-Alanine was not consumed during 70 min of perfusion and its protective action was not inhibited by blocking transamination with 0.5 mM amino-oxyacetate. The protective action of glycine was not inhibited by blocking glycine metabolism with 0.1 mM cysteamine. Thus the beneficial effects of L-alanine and glycine do not require their metabolism. These observations suggest that small neutral amino acids prevent tubular disruption through their physicochemical effects, which can stabilize membrane protein tertiary structure.

Alanine↗

PubMed1990

Functional effects of proximal tubular dopamine production.

Significant proximal tubular responses to exogenous dopamine require 0.1 to 10 mumol/L concentrations but endogenous peritubular dopamine and DOPA concentrations are in the picomolar to nanomolar range. Dopamine concentration approaches micromolar levels within proximal tubular cells and their brush borders, as a result of DOPA decarboxylation and secretion, and in collecting duct fluid, as a result of tubular fluid absorption. Thus dopamine probably acts either within the proximal tubule cell or brush border or from the collecting tubular lumen. DOPA and Na+ uptake are coupled; dopamine uptake is linked to intracellular electrical potential and its secretion to H+ counter-transport; therefore alterations in proximal tubular Na+ and H+ transport influence dopamine excretion. Haloperidol and SCH 23390 block dopamine excretion, therefore dopamine antagonists may inhibit tubular dopamine responses by lowering intracellular dopamine concentration as well as by receptor blockade. Evidence for an intracellular site of dopamine action can be deduced from the inhibitory effect of DOPA on oxygen consumption and 86Rb uptake in proximal tubule cells. We have confirmed these findings in isolated proximal tubule cells but not in proximal tubule fragments. The discrepant responses may be due to the fact that isolated cells loose their polarity while tubule fragments remain polarized. Dopamine inhibition of proximal tubular Na+, K(+)-ATPase is not reproduced by single dopamine agonists or inhibited by dopamine antagonists. Dopamine effects which are not linked to known dopamine receptors may be the result of redox cycling. Micromolar dopamine oxidizes sulfhydryl groups which may modify enzyme structure and activate protein kinase C.

Animals↗

PubMed1989

Multielement analysis of biological samples by inductively coupled plasma-mass spectrometry. I. Preliminary considerations and analysis of rat liver and serum.

Interest in the biological behavior of a growing number of elements, along with increasing recognition of the importance of interactions among them, demands a versatile and reliable technique for multielement analysis of biological samples. Significant improvements over the sensitivity achieved with conventional inductively coupled plasma (ICP) optical emission spectrometries have been realized with the introduction of quadrupole mass spectrometry (MS) for detection of ions in the plasma. The hybrid technique of ICP-MS promises to be a method of rapid multielement analysis, at detection limits that approach or surpass those of other technologies. However, the application of ICP-MS to analyses of biological interest is truly in its infancy. Here we report the use of ICP-MS for the determination of more than 30 elements of biological interest in a tissue and a biological fluid (rat liver and serum, respectively). Experimental values of the elements serve as a basis for discussion of analytical protocols, performance criteria, and certain problems peculiar to ICP-MS.

Animals↗

PubMed1989

Application of a fiber-matrix model to transport in renal tubules.

The effects of tight junction structure on water and solute fluxes across proximal tubular epithelium were examined with fiber-matrix equations previously derived by Curry and Michel (1980. Microvascular Research. 20:96-99). Using plausible estimates of tight junction fiber length and width the model predicts solute (Ps) and water permeability (Lp) coefficients that agree with the measured values. When fiber-matrix and pore models were compared for physiologically relevant ranges of matrix void fraction (80-98%) and pore radii (0-20 A), the fiber-matrix model predicted a 10-fold higher Lp/Ps ratio. Lp/Ps was most sensitive to small changes in tight junction structure when void fractions exceeded 90%. Void fractions of 96.5% and 97.1% predicted previously measured values for Lp and solute permeabilities in rat and rabbit proximal tubules. These values are consistent with void fractions and permeabilities of artificial membranes. The fiber-matrix tight junction model was incorporated into a model of reabsorption from the rat proximal tubule developed by Weinstein (1984). American Journal of Physiology. 247:F848-F862.) A void fraction of 98% predicted the experimental results for isosmotic reabsorption driven by active transport. Changing void fraction over the range of 97-99% produced a 50-75% change in predicted volume reabsorption with active transport. According to the fiber-matrix model: (a) solute permeabilities alone cannot be used to predict Lp, (b) previously measured solute permeabilities in the proximal tubule are compatible with significant water reabsorption through a water-permeable tight junction, and (c) hydraulic and solute permeabilities may be sensitive to small changes in tight junction fiber length and diameter or ionic strength within the tight junction.

Absorption↗

PubMed1989

Renal nerves in the pathogenesis of hypertension: a review.

1. Renal nerve discharge may contribute to renal arteriolar hyperplasia and hypertrophy but the kidney is not the major site of increased vascular resistance in hypertension. 2. Natriuretic and diuretic responses to dietary salt are dissociated in some SS hypertensives. Experiments with perfused rat kidneys indicate that this dissociation is due to circulating catecholamines and not to increased renal nerve activity. 3. Reduced tubular dopamine production may be involved in SS hypertension but decreased dopaminergic nerve activity is not apparent. 4. Increased salt intake initiates a generalized increase in vascular resistance in SS hypertensives. The small amount of salt retained over 5-7 days could not produce the observed increase in blood pressure by altering ECF volumes or transmembrane ion gradients which suggests that a systemic vasoconstrictor, such as renin, is involved. In these patients, inappropriate renal nerve activity could shift the balance between salt intake, blood pressure and renin release since low level renal nerve activity raises the blood pressure required to inhibit renin release. Reversal of SS hypertension with ACE inhibitors is consistent with this hypothesis.

Animals↗

PubMed1988

Neural stimulation of gluconeogenesis in isolated pyruvate-perfused rat kidneys.

To estimate peritubular norepinephrine concentration during renal nerve stimulation, we compared gluconeogenic responses in isolated pyruvate-perfused rat kidneys with electrical nerve stimulation and exogenous norepinephrine. During 2 and 4 Hz stimulation, venous norepinephrine was 1.7 +/- 0.4 and 2.7 +/- 0.9 nmol/L, respectively. Intra-arterial norepinephrine infusion of 60 pmol/min for 20 min (an amount corresponding to that released during 4 Hz stimulation) resulted in venous norepinephrine levels of 3.6 +/- 0.6 nmol/L. Electrical stimuli (1, 2, and 4 Hz) sustained increases in vascular resistance of 2, 5, and 11% during 20 min of stimulation, while the norepinephrine infusion increased resistance gradually by 8% and a bolus (12.5 nmol/L) transiently increased resistance by 2%. All electrical and norepinephrine interventions, except 1 Hz, decreased fractional Cl excretion. Decreased glomerular filtration rate was observed only during 4 Hz stimulation. Gluconeogenesis transiently increased during stimulation at 2 or 4 Hz (12% (p = 0.056) and 15% (p = 0.028]. The 5% increase in gluconeogenesis during norepinephrine infusion did not differ from the increase during 4 Hz stimulation (p = 0.45). An exogenous norepinephrine bolus (12.5 nmol/L) increased gluconeogenesis 60% for 15 min, four time more than the response to 4 Hz nerve stimulation (p = 0.012). Therefore, we conclude that nerve stimulation sufficient to produce sustained vasoconstriction and antinatriuresis raised norepinephrine concentration less than 12 nmol/L on the peritubular surface of the S1 proximal tubule, thus accounting for the small gluconeogenic response.

Animals↗

PubMed1987

Is there a role for renal alpha 2-adrenoceptors in the pathogenesis of hypertension?

Current information suggests that alpha 2-adrenoceptors do not directly influence vascular resistance or Na reabsorption in the rat kidney. To reexamine the effects of alpha 2-agonists we used isolated rat kidneys perfused at 37.5 degrees C with precise measurement of renal artery pressure and flow. The recirculating perfusate contained pyruvate as the sole metabolic substrate which enabled us to use gluconeogenesis as an index of proximal tubular alpha 1-responses. Clonidine and guanfacine in 100 nM concentrations decreased phosphate excretion without altering Na, Cl, or K reabsorption or gluconeogenesis; 500 nM concentrations increased vascular resistance and decreased glomerular filtration rate and Na, Cl, and K excretion with no significant effect on gluconeogenesis. Prior thyroparathyroidectomy prevented the antiphosphaturic but not the antinatriuretic or vascular responses. Clonidine, an alpha 2-agonist with some alpha 1-activity, was a more potent vasoconstrictor than methoxamine or guanfacine. In the presence of prazosin (1 microM), norepinephrine (60 nM) stimulated phosphate reabsorption; norepinephrine alone did not stimulate phosphate reabsorption which indicates alpha 1-antagonism of this alpha 2-response to NE. These results and a literature review suggest that increased renal alpha 2-adrenoceptors could raise renal vascular resistance, reduce renin secretion, and antagonize parathyroid hormone effects on Pi, Ca, HCO3, and Na reabsorption to produce a low renin type of hypertension with increased proximal Na reabsorption and abnormal Ca and Pi excretion.

Adrenergic alpha-Agonists↗

PubMed1987

Specific alpha 1-, alpha 2-, and beta-responses to norepinephrine in pyruvate-perfused rat kidneys.

We compared the effects of alpha- and beta-adrenergic agonists on vascular resistance, gluconeogenesis (GNG), and electrolyte excretion in pyruvate-perfused rat kidneys. Norepinephrine (NE) (15-60 nM) increased vascular resistance (2-19%) and GNG (42-49%) and decreased fractional excretion of Na (18-34%), Cl (38-48%), and K (13-27%). Prazosin and yohimbine blocked the vasoconstrictor but not the antinatriuretic response. Prazosin revealed an antiphosphaturic and inhibited the gluconeogenic response. Propranolol blocked the effect on Na and Cl (66%) and K excretion (100%). Methoxamine (0.6-1 microM) maximally increased GNG (40-52%) with little effect on vascular resistance (+0-9%) and NaCl excretion (-0-11%). Adding glucose to the perfusate increased methoxamine's effects on electrolyte excretion and vascular resistance. Mercaptopicolinate did not alter methoxamine's effects during pyruvate perfusion. Clonidine (0.1 microM) decreased phosphate excretion without vasoconstriction or antinatriuresis; 0.5-1 microM vasoconstricted and decreased NaCl excretion. Isoproterenol (0.1 microM) vasodilated and decreased Na (25%), Cl (40%), and K excretion (20%). Thus alpha 1- and beta-receptors could account for the effect of NE on GNG and K reabsorption, respectively. Synergism of alpha 1, alpha 2, and beta were required for full antinatriuresis. Glucose increased alpha 1-stimulated vasoconstriction and antinatriuresis. Blocking alpha 1-receptors revealed an alpha 2-like antiphosphaturic response.

Animals↗

PubMed1987

Alpha 1-adrenergic stimulation of renal Na reabsorption requires glucose metabolism.

The effect of glucose on renal responses to alpha 1-adrenergic stimulation was examined in isolated rat kidneys perfused with 5 mM lactate, 5 mM alanine, 0.5 mM pyruvate, and 0.2 mM mercaptopicolinic acid. Adding 5 mM glucose to this perfusate vasodilated the kidneys and raised the glomerular filtration rate (GFR) and free water clearance without altering fractional sodium excretion. alpha 1-Adrenergic actions were evaluated with norepinephrine (NE, 60 nM), methoxamine (600 nM), and prazosin (1 microM). Glucose altered neither the vasoconstriction nor the reduction in GFR produced by NE and methoxamine but increased the antinatriuretic responses (P less than 0.001). Glucose was required for prazosin to inhibit the effect of NE on sodium and lithium excretion. The nonmetabolized glucose analogue, alpha-methyl-D-glucoside (5 mM), did not increase the antinatriuretic response to NE, therefore glucose metabolism and not Na cotransport stimulated the alpha 1-adrenergic response. Glucose did not alter alpha 1-adrenoceptor number or binding affinity for prazosin in renal cortical homogenates. We conclude that glucose metabolism in the proximal tubule is involved in the stimulation of sodium reabsorption by alpha 1-adrenoceptor agonists.

Absorption↗

PubMed1986

An active pathway for serotonin synthesis by renal proximal tubules.

Serotonin (5HT) has significant effects on renal metabolism and glomerular function and is a potent renal vasoconstrictor. In this study we describe and localize a highly active biosynthetic pathway for serotonin in the kidney. Rat kidneys were dissected into cortical and medullary fractions; in some experiments the cortex was also separated into subfractions enriched with glomeruli or proximal tubules. Serotonin and tryptophan hydroxylase (TyOH) were measured by radioenzymatic techniques. (table; see text) Renal denervation did not alter tryptophan hydroxylase activity. In kidneys from human cadaveric donors, cortical tryptophan hydroxylase (4.13 +/- 0.68 nM/30 min/g) exceeded that in the medulla (1.96 +/- 0.86 nM/30 min/g). Aromatic L-amino acid decarboxylase, the remaining enzyme for serotonin synthesis, is present in both rat renal cortex and medulla; however, we found 15-fold greater decarboxylase activity in proximal tubular (2070 nM/30 min/g) as compared to glomerular (131 nM/30 min/g) subfractions. We were able to demonstrate that under physiological conditions, free urine serotonin reflects actual biosynthesis by the kidney. Thus, although serotonin stores retained by the kidney appear small and relatively localized to the medulla, the enzymatic activity for the synthesis of serotonin in the kidney is comparable to that in the brain, with the complete pathway localized to renal cortical proximal tubules. These data suggest that further studies of renal serotonin metabolism may contribute to our understanding of renal function in health and disease.

Animals↗

PubMed1986

Neural not tubular dopamine increases glomerular filtration rate in perfused rat kidneys.

We examined the effect of endogenous neural and tubular dopamine production on renal function in isolated perfused kidneys. Nerves and proximal tubules in perfused kidneys produce dopamine from endogenous substrates. Surgical denervation 5-14 days before perfusion removed neural dopamine production and decreased dopamine excretion 32% (P less than 0.05), inulin clearance 7% (P less than 0.05), and sodium excretion 57% (P less than 0.01). Carbidopa, which abolished neural and tubular dopamine production, produced similar functional effects. Haloperidol, Sch 23390, and (+)butaclamol, but not (-)butaclamol, added during perfusion increased renovascular resistance 4-5% (P less than 0.001) and decreased inulin clearance 20% (P less than 0.001). Sch 23390 reduced fractional sodium excretion (P less than 0.01), but haloperidol and butaclamol did not. Chronic denervation or carbidopa blocked the reduction of inulin clearance by haloperidol, but alpha- and beta-adrenergic antagonists did not. Fractional sodium excretion increased after adding haloperidol to denervated or adrenergic blocked kidneys. Denervation blocked the effect of Sch 23390 on inulin clearance but not on sodium excretion. Haloperidol inhibited dopamine excretion. Thus dopamine released from acutely severed nerves in perfused kidneys increases glomerular filtration rate (GFR). Dopamine produced by tubules of chronically denervated kidneys did not influence GFR but stimulated sodium excretion by an Sch 23390-sensitive mechanism.

Adrenergic alpha-Antagonists↗

PubMed1986

Role of 5'-nucleotidase in adenosine-mediated renal vasoconstriction during hypoxia.

Regulation of renal function by endogenous adenosine production was examined in isolated perfused rat kidneys. Reducing perfusate pO2 from 400 +/- 15 to 130 +/- 5 mm Hg for 20 min created an energy deficit and increased adenosine in venous perfusate (0.06 +/- 0.02 to 0.79 +/- 0.15 microM) and snap-frozen renal cortex (5.6 +/- 1.4 to 16.7 +/- 2.7 nmol/g wet wt.). A competitive inhibitor of 5'-nucleotidase, alpha,beta-methyleneadenosine diphosphate (120 microM), inhibited the production of adenosine during hypoxia (perfusate, 0.26 +/- 0.05 microM and renal cortex, 3.1 nmol/g) but did not prevent the decline in cortical tissue ATP and ADP. The inhibitor was concentrated 3-fold in renal cortex compared to perfusate and could therefore inhibit both ecto and endo 5' nucleotidases. Vascular resistance increased 11.1 +/- 0.5% during hypoxia. Inhibition of 5'-nucleotidase reduced the vasoconstrictive response by 40% (P less than .01). An A1 antagonist, 1,3-diprophyl-8-(2-amino-4-chlorophenyl)xanthine (10(-5) M), reduced the effect of hypoxia on vascular resistance by 60% (P less than .005). Adenosine deaminase (7-14 U/ml) added during hypoxia reduced venous adenosine from 1.0 to 0.3 microM and reduced vascular resistance by 3 +/- 1%. Neither the inhibitors nor adenosine deaminase significantly altered the response of glomerular filtration rate or sodium reabsorption to hypoxia. These results indicate that either ecto or endo 5'-nucleotidase controls the renal production of adenosine during an energy deficit and that endogenous adenosine constricts the renal vasculature.

5'-Nucleotidase↗

PubMed1985

Fluorometric determination of adenine nucleotides and adenosine by ion-paired, reverse-phase, high-performance liquid chromatography.

A sensitive and specific assay for measurement of adenine nucleotides and adenosine by paired-ion high-performance liquid chromatography is described. The 1,N6-ethenoderivatives of ATP (epsilon-ATP), ADP (epsilon-ADP), AMP (epsilon-AMP), and adenosine (epsilon-Ado), formed by reaction with chloroacetaldehyde at 37 degrees C, were separated under isocratic conditions in 20 min. These compounds are strongly fluorescent at an emission wavelength of 280 nm, rendering a lowest detection limit of 2-5 pmol per injection. The detector responded linearly over the measured ranges (5-100 pmol for epsilon-Ado and 5-4000 pmol for nucleotides). Specificity was confirmed enzymatically. alpha, beta-Methyleneadenosine 5'-diphosphate could be used as an internal standard for measurement of the nucleotides. Significant amounts of NADH appeared as a separate peak in hypoxic tissue. Recoveries from snap-frozen kidney were 88, 92, 76, and 63% for AMP, ADP, ATP, and adenosine, with SD for recovery of 1.0, 10.5, 8.3, and 5.6%, respectively. This method was successfully used to measure adenine nucleotides and adenosine in oxygenated and hypoxic perfused rat kidneys.

Adenine Nucleotides↗

PubMed1985

Metabolic control of renal vascular resistance and glomerulotubular balance.

Renal vascular resistance (RVR) and glomerulotubular balance were examined in isolated rat kidneys perfused at 100 mm Hg with 10 mM lactate (L) or 10 mM pyruvate (P) or 5 mM glucose (G) either alone or with a mixture of 20 amino acids (13.5 mM, AA); albumin oncotic pressure 24 +/- 1 mm Hg. RVR was L greater than P greater than G = AA. Vasodilation by G and AA was additive. Proximal tubular sodium-cotransport was evaluated from fractional reabsorption (FR) of phosphate (Pi), G, and L. FR Pi was 91% in AA, 86% in P, 72% in L, and 67% in G. Combining AA or P with L or G increased FR Pi to 89 to 90%. FRs of G and L by G and L perfused kidneys were 83 and 78%, respectively, and were increased to 97 to 99% by combining G or L with AA or P. P and AA also increased FR sodium and FR water when combined with L or G or when combined with each other. GFR correlated positively with FR sodium and FR water. AA combined synergistically with L to increase gluconeogenesis. These results indicate that, compared with pyruvate or AA, neither glucose nor lactate alone is a good energy source for proximal tubular reabsorption, that synergistic interactions between AA or pyruvate and lactate or glucose augment GFR by increasing proximal tubular reabsorption, and that the vasodilating effects of glucose and AA are not related directly to their effects on GFR.

Amino Acids↗

PubMed1985

Dopamine production by isolated glomeruli and tubules from rat kidneys.

To locate the sites of dopamine (D) production in rat renal cortex, we separated glomeruli and proximal tubules by sieving or centrifugation in Percoll after collagenase digestion. After centrifugation layer I contained 60-80% glomeruli and 20-40% tubule fragments, half of which did not stain with alkaline phosphatase, layer II contained 0-5% glomeruli, 10-25% tubule fragments other than proximal tubules, and 70-85% proximal tubule fragments. Layer IV contained 85-95% proximal tubules. Gluconeogenic rates were (micromoles per hour per gram wet weight) as follows: I, 4 +/- 1; II, 7 +/- 2; and IV, 16 +/- 1. Norepinephrine (NE) content was (picomoles per gram wet weight) I, 310 +/- 30; II, 540 +/- 40; IV, 195 +/- 60. D content was (picomoles per gram wet weight) I, 26 +/- 6; II, 46 +/- 13; IV, 33 +/- 7. Surgical denervation 4-6 days previously reduced the norepinephrine content of layers I and II to 35 +/- 10 (p less than 0.001) and of IV to 60 +/- 20 (p less than 0.05) and the D content of layers I and II to 13 +/- 6 and 6 +/- 6 pmol/g, respectively (p less than 0.01); D content of layer IV was unchanged. D production from 10(-7) M 3,4-dihydroxyphenylalanine (DOPA) was (nanomoles per gram per minute) I, 0.2 +/- 0.03; II, 0.7 +/- 0.1; IV, 1.0 +/- 0.04. DOPA consumption was (nanomoles per gram per minute) I, 0.6 +/- 0.1; II, 1.4 +/- 0.3; and IV, 1.8 +/- 0.2. Denervation did not change D production or DOPA consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Vagal afferent activity and renal nerve release of dopamine.

To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p less than 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis.

Animals↗

PubMed1984

Dopamine production by the isolated perfused rat kidney.

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 +/- 0.1 ng DA X min-1 X g wet weight-1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 +/- 0.06 ng DA X min-1 X g-1 and denervated kidneys excreted 1.0 +/- 0.07 DA X min-1 X g-1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 +/- 0.1 ng DA X min-1 X g-1 (p less than 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng X min-1 X g-1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 +/- 0.13 ng DA X min-1 X g-1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗