Biomedical subjects

J Schnermann

Publications and source records attributed to J Schnermann.

At least 19 recordsLinked to original sources

PubMed1992

Induction of water diuresis by endothelin in rats.

Experiments were performed in anesthetized rats to examine the possibility that endothelin (ET) modifies renal epithelial function in addition to its well-established hemodynamic actions. Infusion of ET-3 at rates between 34 and 178 ng.kg-1.min-1 was in many cases followed by a rise in urine flow and a persistent decrease in urine osmolality, whereas glomerular filtration rate (GFR) did not significantly change. The extent of ET-induced diuresis was dependent on the response of GFR: in rats in which ET-3 infusion caused a marked reduction of GFR (greater than 70%) ET-induced diuresis was not seen, even though urine osmolality still fell significantly. From animal to animal, ET-induced changes of urine flow or GFR did not correlate significantly with the rate of ET-3 infusion. ET-1, another ET isopeptide, also produced water diuresis when administered in GFR-neutral doses. Urinary excretion of total solutes and of sodium was not significantly altered by ET-3. Infusion of vasopressin blunted the diuretic effect of ET-3, whereas ET-3-induced water diuresis was not measurably altered by chronic or acute treatment with a converting enzyme inhibitor or by acute inhibition of prostaglandin synthesis. Induction of water diuresis was not secondary to an inhibition of vasopressin secretion since it could be demonstrated in homozygous Brattleboro rats in which antidiuresis was produced by the infusion of vasopressin at a rate of 200 microU.kg-1.min-1. These data suggest that ET may be an inhibitory modulator of the hydrosmotic action of vasopressin at the level of the renal collecting duct.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Vasomotor effects of purinergic agonists in isolated rabbit afferent arterioles.

To examine the vasomotor effects of purinergic agonists, experiments were performed in isolated afferent arterioles of rabbit kidneys dissected together with their glomerulus and perfused with a pressure head of 120 cmH2O. Changes in vascular diameter were taken as measure of changes in vasomotor tone. Adenosine caused a dose-dependent and persistent decrease in vascular diameter along the entire afferent arteriole with significant changes being detectable at 10(-8) M. Constrictor effects were more pronounced in the glomerular entrance segment of the arteriole where adenosine caused a progressive diameter reduction with maximum contraction at 10(-4) M. Similar monophasic diameter reductions of the distal afferent arteriole were seen with increasing bath concentrations of 2-chloroadenosine (2-ClAdo), cyclohexyladenosine (CHA), and 5'-(N-ethylcarboxamido)adenosine (NECA). Concentrations to achieve half-maximum responses were 92.5 nM for 2-ClAdo, 39 nM for CHA, and 107 nM for NECA. The A2-receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine had no effect on vessel diameter. Increasing bath concentrations of ATP caused significant diameter reductions in both the proximal and distal parts of the afferent arterioles. Addition of the A1-receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine, eliminated the effect of ATP in the proximal region of the arteriole, but a significant diameter reduction was still seen in the glomerular entrance segment. The ATP analogue, beta gamma-methylene-ATP, caused a significant diameter reduction in this segment. These results are consistent with an essentially exclusive presence of A1 receptors in the glomerular entrance segment of the afferent arteriole, whereas in more proximal regions A2 receptors appear to also be expressed in low density. These studies also provide functional evidence for the presence of P2x receptors in renal afferent arterioles.

Adenosine↗

PubMed1992

Intracellular ATP can regulate afferent arteriolar tone via ATP-sensitive K+ channels in the rabbit.

Studies were performed to assess whether ATP-sensitive K+ (KATP) channels on rabbit preglomerular vessels can influence afferent arteriolar (AA) tone. K+ channels with a slope conductance of 258 +/- 13 (n = 7) pS and pronounced voltage dependence were demonstrated in excised patches from vascular smooth muscle cells of microdissected preglomerular segments. Channel activity was markedly reduced by 1 mM ATP and in a dose-dependent fashion by glibenclamide (10(-9) M to 10(-6) M), a specific antagonist of KATP channels. 10(-5) M diazoxide, a K+ channel opener, activated these channels in the presence of ATP, and this effect was also blocked by glibenclamide. To determine the role of these KATP channels in the control of vascular tone, diazoxide was tested on isolated perfused AA. After preconstriction from a control diameter of 13.1 +/- 1.1 to 3.5 +/- 2.1 microns with phenylephrine (PE), addition of 10(-5) M diazoxide dilated vessels to 11.2 +/- 0.7 microns, which was not different from control. Further addition of 10(-5) M glibenclamide reconstricted the vessels to 5.8 +/- 1.5 microns (n = 5; P less than 0.03). In support of its specificity for KATP channels, glibenclamide did not reverse verapamil induced dilation in a separate series of experiments. To determine whether intracellular ATP levels can effect AA tone, studies were conducted to test the effect of the glycolytic inhibitor 2-deoxy-D-glucose. After preconstriction from 13.4 +/- 3.2 to 7.7 +/- 1.3 microns with PE, bath glucose was replaced with 6 mM 2-deoxy-D-glucose. Within 10 min, the arteriole dilated to a mean value of 11.8 +/- 1.4 microns (n = 6; NS compared to control). Subsequent addition of 10(-5) M glibenclamide significantly reconstricted the vessels to a diameter of 8.6 +/- 0.5 micron (P less than 0.04). These data demonstrate that KATP channels are present on the preglomerular vasculature and that changes in intracellular ATP can directly influence afferent arteriolar tone via these channels.

Adenosine Triphosphate↗

PubMed1991

Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport.

Transport inhibitor and ion substitution studies were performed using perfused, superfused preparations of the isolated rabbit juxtaglomerular apparatus to investigate transport dependency of macula densa-mediated renin secretion. In the first experimental series, tubular perfusion with a high-NaCl solution containing 10(-6) M bumetanide increased renin secretion compared with perfusion with high NaCl alone from 8.7 to 24.6 nano-Goldblatt hog units (nGU)/min. Bath addition of 10(-6) M bumetanide had no effect on renin release. The second series tested ability of luminal addition of 54 mmol/l Na or Cl salts to inhibit renin secretion, starting from a stimulated value produced by low-NaCl perfusion. Perfusion with a high-NaCl solution decreased renin secretion from 58.9 to 14.8 nGU/min, which served as a positive control. Addition of choline chloride decreased renin secretion from 42.7 to 16.6 nGU/min, and RbCl decreased renin secretion from 54.9 to 17.0 nGU/min. In contrast, addition of two different Na salts had no effect on renin release (from 41.7 to 31.6 nGU/min with sodium isethionate and from 14.1 to 13.5 nGU/min with sodium acetate). Also, in the presence of 26 mmol/l Cl, addition of 54 mmol/l Na had no effect on renin secretion (29.9-36.8 nGU/min). These data demonstrate that renin secretion is directly stimulated by luminal application of transport blockers and can be inhibited by increases in Cl concentration at the macula densa but not by changes in Na concentration. These results support the hypothesis that the initiating signal for macula densa control of renin secretion is an inverse change in transport rate via the luminal Na(+)-K(+)-2Cl- cotransporter.

Animals↗

PubMed1991

Vasoconstrictor effect of angiotensin and vasopressin in isolated rabbit afferent arterioles.

The present studies were performed to examine the vasoconstrictor effect of angiotensin II (ANG II), angiotensin III (ANG III), and vasopressin in isolated afferent arterioles of the rabbit kidney. Afferent arterioles were dissected together with their glomerulus and perfused with a pressure head of 120 cmH2O. Changes in vasomotor tone were assessed as diameter changes on videotaped recordings. Afferent arterioles responded to the angiotensins and vasopressin with dose-dependent reductions in vascular diameters with half-maximum responses being observed at concentrations between 10(-9) and 10(-8) M. Responses to ANG II and III were inhibited by saralasin. Contractile responses to ANG II and vasopressin were not altered by prior occlusion of the efferent arteriole, suggesting that afferent vasoconstriction does not represent a myogenic reaction to an increase in efferent resistance. The vasoconstrictor response to ANG II was largely eliminated by removal of the glomerulus and the distal-most portion of the afferent arteriole, whereas the response to vasopressin remained intact. Our data are consistent with the notion that the juxtaglomerular apparatus (JGA) and/or glomerulus may control proximal afferent arteriolar contractility by electrotonic or myogenic coupling mechanisms or by producing cofactors that modulate vasomotor responses.

Angiotensin II↗

PubMed1991

Direct vasoconstriction as a possible cause for amphotericin B-induced nephrotoxicity in rats.

In anesthetized rats we tested the hypothesis that amphotericin B (AmB) reduces glomerular filtration rate (GFR) by activating the tubuloglomerular feedback (TGF) mechanism. Infusion of 1 mg/kg AmB over 50 min was followed by a reduction in kidney GFR (from 0.47 +/- 0.03 to 0.39 +/- 0.02 ml/min per 100 g body wt during the second hour after infusion; P less than 0.05) and by an increase in urine flow and urinary chloride excretion. Single-nephron GFR (SNGFR) measured in proximal (TGF interrupted) or distal tubules (TGF intact) decreased to a similar degree from 33.4 +/- 1.8 and 30.6 +/- 1.2 nl/min in the control period to 19.7 +/- 1.9 and 21.2 +/- 1.6 nl/min during the second hour after AmB infusion (P less than 0.05). Distal chloride concentrations and TGF responses to changes in loop of Henle flow rate were not significantly altered by AmB. AmB at 10(-5) M reduced the diameter of isolated perfused afferent arterioles from rabbit kidneys. In isometrically contracting rings of rabbit aorta and renal artery in vitro AmB produced endothelium-independent constriction, with half-maximal contraction (EC50) being achieved by 1.8 x 10(-6) and 2.6 x 10(-6) M in intact vessels and 1.3 x 10(-6) and 1.7 x 10(-6) M in endothelium-denuded vessels respectively. Tension development did not occur in Ca-free media or in the presence of Ca channel blockers. Pretreatment with ouabain or Bay K 8644 potentiated the effect of AmB. The vasoconstrictive effect of AmB was counteracted by aminophylline and atrial natriuretic peptide. We conclude that the AmB-induced reduction in GFR is not caused by TGF activation and that AmB has a direct vasoconstrictor effect that is probably initiated by depolarization-induced opening of Ca channels. This effect may be an important component of the nephrotoxic actions of AmB.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1991

The afferent arteriole--the target for macula densa-generated signals.

The contractile characteristics of the afferent arteriole revealed in the present series of experiments lead one to predict that TGF-induced vasoconstriction should be dependent on both A-II and adenosine. In fact, previous evidence has suggested a role for both adenosine and angiotensin in the TGF mechanism. Acceleration of adenosine deamination as well as adenosine receptor blockade markedly reduced the effect of distal NaCl concentration on SNGFR or PSF. Conversely, inhibition of adenosine breakdown or cellular adenosine uptake, two interventions which are likely to increase interstitial adenosine levels, augmented TGF responses. The same effect was seen when adenosine1-receptor analogs were locally applied by microinfusion. The administration of A-II-converting-enzyme blockers or A-II-receptor antagonists reduced TGF responses, while peritubular or intravenous administration of A-II augmented them. Furthermore, the inhibition of TGF responses caused by volume expansion-induced reductions in plasma A-II concentrations could be restored to normal by A-II infusion. The present results raise the possibility that normal TGF responsiveness depends upon the availability of both adenosine and A-II in sufficiently high concentrations. Figure 1 outlines a mechanism of this mutual dependency. One may assume that adenosine is generated as a consequence of NaCl-dependent changes in NaCl transport by macula densa cells or by TALH cells in the immediate vicinity of the macula densa. The absence of capillaries in the juxtaglomerular interstitium could permit an accumulation of the autacoid to an extent not possible in other regions of the renal interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1990

Cellular mechanisms within the juxtaglomerular apparatus.

The tubular-vascular connection via the juxtaglomerular apparatus appears to serve two functions, local control of renal vascular resistance and regulation of renin secretion. A fall in single nephron glomerular filtration rate (SNGFR) and an increase in resistance are produced by an increase in NaCl concentration at the macular densa. This change also results in inhibition of secretion of renin. The macula densa has a unique location near the terminal end of the thick ascending limb, where NaCl concentration is highly flow dependent. The cellular mechanisms by which changes in tubular fluid NaCl produce vasoconstriction and inhibition of renin secretion are unknown, but the anatomy of the juxtaglomerular apparatus strongly suggests that such responses may be mediated by the extraglomerular mesangial cells located in the polar cushion underlying the macula densa. Recent evidence suggests that interstitial chloride concentration in this compartment may be quite variable, and that increases in external chloride may enhance the activation of the mesangial cell.

Feedback↗

PubMed1990

Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade.

Experiments were performed in anesthetized rats to study the effect of the selective adenosine1 (A1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on tubuloglomerular feedback (TGF) responses assessed as the maximum change of stop-flow pressure (PSF). Compared with control, PSF responses were reduced during luminal application of CPX at 10(-4) and 10(-5)M (-4.9 +/- 0.44 vs. + 0.9 +/- 0.42 mmHg and -6.8 +/- 0.69 vs. -1.4 +/- 0.7 mmHg, respectively), during peritubular administration of CPX at 10(-4)M (-6.2 +/- 0.44 vs. -2.8 +/- 0.42 mmHg), and during infusion of CPX at 10(-4) M into the lumen of a neighboring nephron (-5.6 +/- 0.6 vs. -1.98 +/- 0.51 mmHg). Selectivity of CPX was tested by studying its effect on the PSF reduction produced by the A1-receptor agonist N6-cyclohexyladenosine (CHA). CHA at 10(-5)M reduced PSF when infused into the peritubular blood (-11.8 +/- 3.7 mmHg), and this effect was blunted by luminal application of CPX (-1.5 +/- 0.6 mmHg). CHA also reduced PSF when infused into a neighboring nephron, and this effect was blunted by infusing CPX at 10(-4)M into the same neighboring nephron, a different neighboring nephron, or a peritubular capillary. These results are consistent with the concept that activation of A1-receptors on vascular cells of the afferent arterioles participates in the mediation of TGF responses.

Adenosine↗

PubMed1990

Effect of dopamine on the tubuloglomerular feedback mechanism.

Experiments were performed in anesthetized rats to examine whether infusion of dopamine is associated with a reduction in the tubuloglomerular feedback (TGF) response of stop-flow pressure (PSF) and early proximal flow rate (VEP) to increases of loop of Henle flow. The purpose of these studies was to test further the validity of the proposal that renal vasodilation is a nonspecific cause for diminished TGF responsiveness. When femoral arterial pressure was kept constant with a suprarenal aortic clamp, intravenous infusion of dopamine at rates of 4, 15, 35, and 75 micrograms.kg-1.min-1 induced a 10.9, 23.4, 31.3, and 30.1% decrease in renal vascular resistance. Maximum PSF and VEP responses were significantly reduced at all dose levels of dopamine, whereas V1/2, the flow rate required to produce the half-maximum response, was not altered. TGF blunting occurred within less than 10 min after starting the dopamine infusion. Peritubular infusion of dopamine reduced maximum PSF responses from 8.8 +/- 0.7 to 4.6 +/- 0.53 mmHg at 10(-4) M (P less than 0.01) and from 6.0 +/- 1.19 to 3.6 +/- 0.55 mmHg at 10(-3) M (P less than 0.05). The results are consistent with the notion that renal vasodilatation may modify TGF responses by preventing the full vasoconstrictor response to changes in luminal NaCl concentration.

Animals↗

PubMed1990

Characterization of the macula densa stimulus for renin secretion.

These studies utilize the isolated perfused rabbit juxtaglomerular apparatus (JGA) to study the macula densa signal for renin secretion in the absence of the confounding influences of intravascular pressure and renal nerve activity. In the first experimental series, JGAs were perfused alternately with high- and low-NaCl solutions to determine the reversibility of the renin response to changes in NaCl concentration. Compared with high-NaCl controls, perfusion with a low-NaCl solution resulted in a fivefold increase in renin secretion rate (RSR) [2.1-10.0 nano-Goldblatt hog units (nGU)/min], and this response was largely reversible. When the solutions were presented in the reverse order, a similar inhibition by high NaCl was observed. In the second series, JGAs were perfused with high-, medium-, and low-NaCl solutions to determine the sensitive range of the renin response to NaCl concentration changes. The full renin response (3.2-16.6 nGU/min), similar in magnitude to that seen in series 1, was found to occur between 80 and 24 mM for Na+ and 61 and 7 mM for Cl-. In the third series, the NaCl concentration and flow rate of the perfusate were altered independently to separate the effects of flow rate, NaCl delivery, and NaCl concentration on RSR. Although a decrease in perfusate flow rate slightly increased RSR (3.4-8.1 nGU/min), a comparable decrease in NaCl concentration resulted in a much higher RSR (26.3 nGU/min). We conclude that in this preparation 1) RSR responds equally to both increases and decreases in macula densa NaCl concentration, and these changes are rapid and largely reversible, 2) the full renin response occurs within the concentration range normally occurring at the macula densa, i.e., below 80 mM Na+ and 61 mM Cl-, and 3) RSR responds with a larger change to alterations in NaCl concentration than in NaCl delivery or fluid flow rate.

Animals↗

PubMed1990

Restoration of tubuloglomerular feedback in volume-expanded rats by angiotensin II.

Experiments were performed in anesthetized rats to examine whether angiotensin II corrects the attenuation of tubuloglomerular feedback (TGF) responses produced by acute extracellular volume expansion. Volume expansion was achieved by an infusion of isotonic saline at a rate of 9 ml/h. When urine flow had stabilized, an increase in loop of Henle flow from 0 to 45 nl/min caused a fall in stop-flow pressure (PSF) by 3.7 +/- 0.3 mmHg and in single-nephron glomerular filtration rate (SNGFR) by 5.1 +/- 1.7 nl/min. During continued saline administration angiotensin II was infused at 16, 48, or 96 ng.kg-1.min-1 while renal arterial pressure was held constant by suprarenal aortic clamping. The mean responses of PSF increased to 5.9 +/- 0.6, 9.8 +/- 0.7, and 14.9 +/- 1.7 mmHg. Angiotensin II infused at 54 ng.kg-1.min-1 increased the SNGFR response to 15.1 +/- 2.1 nl/min, whereas kidney GFR and distal SNGFR fell. Subcapsular pressure was not significantly altered by angiotensin II infusion (16 ng.kg-1.min-1). Plasma angiotensin (y, pg/ml) as a function of angiotensin II infusion rate (x, ng.kg-1.min-1 for approximately 20 min) was found to fit the function y = 2.89 + 3.53x. An infusion of approximately 15 ng.kg-1.min-1 restored plasma angiotensin levels in the volume-expanded rats to hydropenic values. These data confirm that angiotensin II may play a role as a physiological regulator of TGF sensitivity.

Angiotensin II↗

PubMed1990

Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus.

Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath. Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M) in the bathing solution and in vehicle control experiments. The control response to increasing luminal NaCl concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P less than 0.01). It is concluded that A1-receptors are located within the JGA, and that A1-receptor activation inhibits renin release. A high NaCl concentration at the macula densa appears to influence A1-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion.

Adenosine↗

PubMed1990

Effect of angiotensin and other pressor agents on tubuloglomerular feedback responses.

Experiments were performed in anesthetized rats to examine the effect of an intravenous infusion of norepinephrine or vasopressin on the tubuloglomerular feedback (TGF) response of stop flow pressure (PSF). During infusion of norepinephrine at an average rate of 107.5 ng/kg min, mean femoral arterial pressure (MAP) increased from 102.1 +/- 3.55 to 113.7 +/- 3.44 mm Hg and PSF-max increased from 7.45 +/- 1.13 to 9.95 +/- 1.19 mm Hg. When MAP was returned to control by a suprarenal aortic clamp PSF-max was 5.64 +/- 1.09 mm Hg (NS vs. control). Similarly, at an infusion rate of 226.5 ng/kg min PSF-max was not significantly different from control (6.79 +/- 1.61 mm Hg). V1/2, the half-maximum flow rate, was not altered by norepinephrine whether MAP increased or was kept constant. Infusion of vasopressin at the pressor dose of 13.0 mU/kg min increased MAP by about 25 mm Hg and raised PSF-max from 6.56 +/- 0.84 to 14.45 +/- 1.54 mm Hg. However, when MAP was returned to normal PSF-max was 5.41 +/- 0.75 mm Hg (NS). Our data show that in contrast to angiotensin II, norepinephrine and vasopressin do not augment TGF responses when a rise in MAP is prevented. Angiotensin II appears to play a specific role in altering the sensitivity of the TGF mechanism.

Angiotensin II↗

PubMed1989

Interaction between loop of Henle flow and arterial pressure as determinants of glomerular pressure.

Experiments were performed in anesthetized rats to study the relationship between loop of Henle perfusion rate, arterial pressure, and stop-flow pressure (SFP) as an index of glomerular capillary pressure. In one set of experiments we measured the SFP feedback response to changes in loop perfusion at three levels of arterial pressure. The maximum SFP response fell significantly from 13.1 +/- 1.44 to 8.14 +/- 1.72 and 3.13 +/- 0.76 mmHg when arterial pressure was reduced from 118.1 +/- 1.27 to 98.8 +/- 0.51 and 78.8 +/- 1.72 mmHg. In other experiments arterial pressure was altered while loop perfusion rate was fixed at one of three levels. Without loop perfusion SFP changed with a slope of 0.27 +/- 0.04 mmHg/mmHg in the arterial pressure range between 80 and 130 mmHg. During perfusion at the flow rate at which response is half maximum, the slope was significantly reduced to 0.12 +/- 0.04. During perfusion at 45 nl/min, it was 0.03 +/- 0.05, a value not significantly different from zero. During dopamine administration (70 micrograms/kg min) SFP was pressure-dependent even during loop perfusion at 45 nl/min. These results show that arterial pressure determines TGF responsiveness and that the TGF signal determines the range of a regulatory input that is directly dependent on arterial pressure.

Animals↗

PubMed1989

Single nephron comparison of the effect of loop of Henle flow on filtration rate and pressure in control and angiotensin II-infused rats.

Experiments were performed in control and angiotensin II-infused rats to test whether the tubuloglomerular feedback responses of early proximal flow rate (VEP) and stop flow pressure (PSF) are elicited by the same flow rate changes. Paired measurements in the same nephron revealed that VEP responses were shifted to the left compared to those of PSF. The flow rate at which the response was half maximum, V1/2, was 14.7 +/- 1.25 nl/min for VEP and 18.9 +/- 0.97 nl/min for PSF (p less than 0.05). This difference in flow dependency was abolished by angiotensin II infusion (V1/2 was 14.6 +/- 0.87 nl/min for VEP and 15.4 +/- 1.09 nl/min for PSF). Furthermore, angiotensin infusion markedly augmented the feedback response magnitude.

Angiotensin II↗

PubMed1988

Renal disease and the development of hypertension in salt-sensitive Dahl rats.

To elucidate the role of the kidneys in the development of hypertension in Dahl salt-sensitive (S), as compared to resistant (R) rats of the JR strain, we analyzed functional and morphological changes before and after the administration of an 8% NaCl diet and the onset of hypertension. The diet was begun at six weeks of age and was continued until 12 weeks of age. At six weeks, blood pressure was not different between S and R rats. Hypertension occurred in S rats receiving the 8% NaCl diet at week 8, and in S rats receiving 0.9% NaCl at week 10. Albuminuria and proteinuria were found in S rats prior to the 8% NaCl diet and progressed regardless of diet. Electron microscopy of glomeruli revealed segmental loss of epithelial foot processes in S rats at six weeks prior to the 8% NaCl diet. Mesangial widening, arteriolar myo-intimal cell hyperplasia and interstitial fibrosis occurred in all S rats. Inulin and PAH clearances in S rats decreased with time, the changes being accelerated by the 8% NaCl diet. Micropuncture of S and R rats prior to the 8% NaCl diet revealed no glomerular hypertension in S rats. The number of glomeruli in S and R rats were not different. We conclude that prehypertensive S rats of the JR strain already have albuminuric glomerular disease not associated with reduced number of glomeruli or glomerular hypertension. The renal pathology is accelerated once hypertension develops. A lower NaCl intake delays, but does not prevent renal disease in S rats.

Albuminuria↗

PubMed1988

Effect of dopamine antagonists on the urine flow of rats infused with hypotonic saline.

1. The probable involvement of dopamine in the regulation of water excretion was investigated by administering dopamine antagonists intravenously to barbiturate--anaesthetized rats undergoing a water diuresis induced by the infusion of 0.83% glucose with 0.3% NaCl at the rate of 9 ml h-1. 2. Administration of 100 micrograms of the D1-/D2-dopamine antagonist, haloperidol, reduced the enhanced urine flow of rats infused with the hypotonic solution by 69% (from 75.4 +/- 13.0 to 23.6 +/- 6.0 microliter min-1, P less than 0.01). Similarly, the D1-receptor antagonist, SCH 23390, reduced urine flow by 58% (from 77.5 +/- 9.2 to 32.7 +/- 7.2 microliters min-1, P less than 0.01) and the D2-receptor antagonist, sulpiride, by 47% (from 66.2 +/- 8.6 to 35.1 +/- 6.8 microliter min-1, P less than 0.05). 3. The injection of SCH 23390 increased the urine osmolality from 189.6 +/- 27.5 to 479.8 +/- 45.8 mosm kg-1 (P less than 0.05). There was no significant change in sodium and potassium excretion in any of the experiments. Blood pressure (BP) decreased after haloperidol and SCH 23390 injection from control values of 121.7 +/- 1.7 and 116.5 +/- 7.4 to 113.3 +/- 3.3 and 106.0 +/- 8.8 mmHg respectively (P less than 0.05). 4. To study whether the influence of dopamine antagonists on urine flow during water diuresis depends on antidiuretic hormone (ADH), we administered 0.6 micrograms d(CH2)5-D-Phe-Ile-AVP (an ADH antagonist) shortly after the injection of 100 micrograms SCH 23390. The preferential V2 ADH-antagonist abolished the antidiuretic effect of SCH 23390 but did not affect its blood pressure reducing effect (from 118.6 +/- 5.6 to 103.2 +/- 4.6 mmHg, P <0.01). 5. These results suggest that dopamine antagonists blunted the hypotonic saline-induced diuresis by favouring ADH release through an interference with an inhibitory dopaminergic pathway.

Animals↗