Biomedical subjects

J D Conger

Publications and source records attributed to J D Conger.

At least 19 recordsLinked to original sources

PubMed1995

Interventions in clinical acute renal failure: what are the data?

A variety of therapeutic approaches have been used both to prevent acute ischemic and nephrotoxic renal injury and to improve renal function and reduce mortality once acute renal failure (ARF) has developed. Unfortunately, there have been few rigorous assessments of the efficacy of these treatment interventions. The reasons for the lack of abundant critical data regarding treatment effects in ARF are several. First, ARF is a functional disorder. It has a spectrum of etiologies, occurs in a variety of clinical settings and varies in severity. Second, selected endpoints of treatment success vary and co-morbid factors frequently determine outcome. Third, it had been difficult to carry out prospective controlled studies in a disorder in which the mortality rate approaches 50%. In this review, an effort was made to analyze the available literature with a primary focus on controlled studies to determine significant prophylactic and treatment effects of various interventions in ARF. Three endpoints of therapy (change in renal function, change in course of azotemia, and change in mortality) were examined for pharmacologic agents. Changes in course of azotemia and mortality were assessed in evaluating different dialysis modes. Effect on nitrogen balance, change in course of azotemia, and change in mortality were used as endpoints to determine treatment effects of different nutritional regimens. When weight was given to prospective controlled studies, some insights emerged as to treatment interventions that are most likely to have beneficial effects in specific settings of ARF. Among pharmacologic agents, mannitol appears to have a positive prophylactic effect in kidney transplantation. There are no other significant beneficial effects of diuretics for prophylaxis or as treatment in early or established ARF. Of vasoactive agents, there is a relatively small amount of data suggesting that diltiazem may have a positive prophylactic effect in kidney transplantation, and dopamine possibly is beneficial early in the evolutionary phase of ARF. Atrial natriuretic peptide and calcium channel blockers may have beneficial effects in established disease. No other pharmacologic interventions are supported by substantial data. At best, the results are equivocal regarding the use of early and vigorous dialysis in ARF. However, there are recent impressive data indicating that the use of biocompatible membranes is efficacious in recovery and survival. There is no clear evidence that one form of nutritional therapy has advantages over others, but some level of amino acid supplementation in addition to basic energy replacement is supported by the overall data.

Acute Kidney Injury↗

PubMed1995

Is parenteral nutrition therapy of value in acute renal failure patients?

A patient with oliguric acute renal failure (ARF) following mitral valve surgery is presented. The patient was treated with parenteral nutrition and hemodialysis. While the patient survived, there were several complications of nutrition therapy. In this review, the benefits, risks, and uncertainties regarding parenteral nutrition in ARF are considered. First, the differences in metabolism in complicated and uncomplicated acute uremia are discussed. The important roles of alterations in intermediary metabolism and of proteases in the catabolism of ARF are emphasized. The historical basis of parenteral nutrition treatment in ARF is reviewed. The results are divided regarding the relationship among nutritional support, improvement in renal function, and enhanced patient survival. A critical analysis of nitrogen metabolism results reported in the literature does not convincingly support the effectiveness of parenteral nutrition formulae in generating positive nitrogen balance. The complications of parenteral nutrition therapy are outlined. In light of the uncertain efficacy and recognized risks of prolonged parenteral nutrition, a rationale for approaching therapy is presented that is based on the estimated metabolic stress and protein-energy requirements of the individual ARF patient.

Acute Kidney Injury↗

PubMed1994

Sequential agonist activation and site-specific mediation of acute cyclosporine constriction in rat renal arterioles.

Evidence suggests that acute and chronic cyclosporine (CsA) nephropathy may be related to its renal vasoconstrictor effects. While the mechanism of CsA-induced renal vasoconstriction is uncertain, several studies indicate that endogenous constrictor agonists including endothelins (ET), platelet activating factor (PAF), and thromboxane A2 (TXA2) play a mediating role. In this study, two possible mechanisms explaining the participation of multiple constrictor agonists in CsA vasoconstriction were investigated: sequential activation of agonists initiated by CsA and site-specific mediation of CsA constriction by different agonists. The acute constrictor effects of CsA were examined in isolated rat renal afferent (AA) and efferent arterioles (EA) without and with specific receptor antagonists of ETA (BQ123, 10(-7) M), PAF (L-659,989, 10(-7) M), and TXA2/PGH2 (SQ29,548, 10(-7) M) in the bathing media. Both BQ123 and L-659,989 completely inhibited CsA, constriction in AA, but had no significant inhibiting effect in EA. Constriction to ET-1 was also blocked by the PAF antagonist L-659,989 in AA, but not EA. There was no effect of SQ29,548 on CsA constriction in AA--however, there was partial attenuation of CsA constriction in EA. Based on these results in isolated rat renal arterioles, it is suggested that CsA-induced constriction in AA is likely mediated by sequential activation of ET and PAF. However, CsA constriction of EA involves a different mechanism or mediator that, in part, may involve TXA2/PGH2 stimulation.

Animals↗

PubMed1994

Endothelial regulation of vascular tone.

Through the release of a variety of relaxing and contracting factors, including nitric oxide and endothelin-1, the endothelium exerts a complex paracrine influence on vascular smooth muscle cells. Dysfunction of these mechanisms for regulating tone may have relevance to various clinical entities, including hypertension, atherosclerosis, renal failure, and diabetes.

Arteriosclerosis↗

PubMed1994

Glomerular and tubular factors in urine flow rates of acute renal failure patients.

Distinguishing between oliguric and nonoliguric acute renal failure (ARF) has clinical relevance. However, there is a paucity of data regarding the pathophysiologic basis for variations in urine flow rates in ARF. This study was designed to determine whether differences in residual levels of glomerular filtration rate (GFR) or differences in tubular reabsorption of filtered solutes and H2O accounted for the variations in urine flow rates among ARF patients. Twenty-five patients with ARF of 3 to 6 days duration having ischemic and nephrotoxic etiologies, increasing serum creatinines of more than 0.7 mg/dL/d, urine sodium concentrations and fractional excretions of sodium (FENa) of more than 20 mEq/L and more than 1%, respectively, 12 hours after stopping diuretics and urine sediments consistent with acute tubular necrosis were studied. Urine and serum collections were made over an 8-hour period to determine creatinine clearance (Ccr), filtered osmolar load, urine to serum creatinine ratio (U/Scr), urine to serum creatinine osmolality (U/Sosm), and FENa. These were compared with urine flow rates. Creatinine clearance was validated as an estimate of GFR in ARF with simultaneous inulin clearances x 12 measurements (r = 0.935, P < 0.001). Residual Ccr was strongly correlated with urine flow rate (r = 0.857, P < 0.001), as was filtered osmolar load (r = 0.810, P < 0.001). However, the latter relationship was totally dependent on Ccr. There was no correlation between U/Scr, U/Sosm, or FENa and urine flow rates. It is concluded that the residual level of GFR is the primary determinant of variations in urine flow rate in patients with ARF.

Absorption↗

PubMed1994

Effects of atrial natriuretic peptide in clinical acute renal failure.

Fifty-three consenting patients meeting clinical and urine composition criteria for established intrinsic ARF were assigned to two treatment groups. Group I patients were treated with human atrial natriuretic peptide (ANP) with or without diuretics. Groups II patients were treated with or without diuretics and with no ANP. Age, sex, etiology of ARF, entry serum creatinines (SCr) (Group I, 5.3 +/- 1.8; Group II, 5.1 +/- 2.1 mg/dl) and creatinine clearances (CCr) (Group I, 9.9 +/- 2.1; Group II, 9.2 +/- 2.1 ml/min) were similar. Thirty patients received ANP [0.20 micrograms/kg/min i.v. x 24 hr (N = 20) or 0.08 micrograms/kg/min i.a. x 8 hr (N = 10)] and furosemide, 0.5 mg/kg/hr x 24 hr or mannitol, 12.5 g every six hours x 4, or no diuretic; 23 Group II patients received diuretics as above or no diuretic in a similar distribution to Group I. CCr (verified with simultaneous inulin clearances x 12, r = 0.93, P < 0.001) increased significantly by eight hours of ANP treatment to 17.1 +/- 3.2 ml/min and by 24 hours after discontinuing ANP to 21.0 +/- 4.4 ml/min (both P < 0.05). There was no corresponding increase in CCr in Group II. Dialysis was required in 23% of Group I and in 52% of Group II patients (different at P < 0.05). Mortality rates of 17% for Group I and 35% for Group II were not significantly different (P = 0.11). It is concluded that parenteral ANP increases CCr and reduces need for dialysis in patients with established intrinsic ARF.

Acute Kidney Injury↗

PubMed1994

Responses to hemorrhagic arterial pressure reduction in different ischemic renal failure models.

Renal blood flow (RBF) autoregulation has been found to be impaired in both norepinephrine (NE) and renal artery clamp (RAC) rat ischemic acute renal failure models. However, the decline in RBF at the normal lower limit of autoregulation is greater in NE-ARF. The present study was designed to determine if this difference in autoregulatory profiles has potential functional and morphologic significance. After demonstrating a fall in RBF to renal perfusion pressure reduction to 90 mm Hg that was twofold more in one week NE- than RAC-ARF (p < 0.001), separate rats of both ischemic ARF types with nearly identical levels of azotemia and glomerular filtration rate reduction and sham-ARF rats were subjected to four-hour controlled reduction in mean arterial pressure to 90 by transient phlebotomy at one week. On day 9, two days after mean arterial pressure reduction, blood urea nitrogen (BUN), serum creatinine (SCr) and creatinine clearance (CCr) showed continued improvement in RAC-ARF, but there were significant increases in BUN (46 +/- 22 to 72 +/- 10 mg/dl) and SCr (1.2 +/- 0.2 to 1.5 +/- 0.2 mg/dl) and a decline in CCr (0.434 +/- 0.127 to 0.334 +/- 0.079 ml/min) in the NE-ARF group (all P < 0.02). The mean sum of scores of morphologic indices of ARF was higher in NE- than RAC-ARF kidneys of rats sacrificed on day 9 but interstitial edema was the only individual index that was worse in NE-ARF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1994

Effects of ANG II, ETA, and TxA2 receptor antagonists on cyclosporin A renal vasoconstriction.

The renin-angiotensin system, endothelin (ET), and vasoconstrictor prostaglandins have been reported in separate studies to mediate the renal vasoconstrictor effect of cyclosporin A (CsA). However, direct comparison of the relative importance of these potential mediators has not been performed. In this study, the attenuating effects of comparable agonist-inhibiting doses of receptor antagonists for angiotensin II (ANG II), DuP-753 at 2.5 mg/kg, for ETA, BQ-123 at 0.5 mg/kg, and for thromboxane A2 (TxA2), SQ-29,548 at 1.6 mg.kg-1.h-1, or saline vehicle on acute CsA (20 mg/kg) renal vasoconstriction were compared in anesthetized Sprague-Dawley rats. All three receptor antagonists significantly limited the CsA-induced increase in renal vascular resistance; however, BQ-123 and SQ-29,548 were more effective than DuP-753. Because all three receptor antagonists demonstrated at least some attenuation of CsA-induced renal vasoconstriction, the potential role of acute CsA-related nitric oxide synthase (NOS) inhibition and nonspecific heterologous effects of specific receptor antagonists on other agonists were determined to exclude the possibilities that there was a general increased agonist sensitivity and that detection of a single or primary constrictor mediator was obscured by "crossover" receptor antagonist effects. CsA significantly reduced renal blood flow (39%) in the presence of the NOS inhibitor, N omega-nitro-L-arginine methyl ester, and there was negligible indication that receptor antagonists had nonspecific effects. It is concluded that CsA-induced renal vasoconstriction is complex and involves activation of multiple constrictor agonists independently or sequentially.

Angiotensin Receptor Antagonists↗

PubMed1993

Analysis of the repertoire of human B-lymphocytes specific for type A and type B blood group terminal trisaccharide epitopes.

Naturally occurring serum antibodies specific for the A and B blood group isoantigens are of great importance in medicine. By using A-type terminal trisaccharide (ATS) or B-type terminal trisaccharide (BTS) coupled to albumin as coating antigens, an enzyme-linked immunosorbent assay capable of detecting all ATS/BTS-binding antibodies was performed. The combination of this enzyme-linked immunosorbent assay with limiting-dilution methodology, using a polyclonal B-lymphocyte activator, permitted a monoclonal analysis of the human antibody repertoire that is specific for ATS and BTS in persons of different blood types. Most (78%) positive supernatants from type O cultures were monospecific for either ATS or BTS, and these were present at roughly equivalent frequencies. Nine supernatants with reactivity toward both ATS and BTS were tested by red cell adsorption; six had properties expected for true dually reactive monoclonal antibodies: adsorption with either A1 or B red cells eliminated both anti-ATS and anti-BTS activity. This finding accords with a monoclonal origin for anti-A,B. The analysis of cultures of peripheral blood lymphocytes from type A and B donors unexpectedly showed significant numbers of clones with apparent autospecificity. However, none of the anti-ATS-positive supernatants from type A cultures or anti-BTS-positive supernatants from type B cultures were adsorbable with A1 or B red cells, respectively. Consideration of only true (adsorbable) positives indicates that the type A and B anti-trisaccharide repertoires differ significantly from the type O repertoire, probably as a result of the action of normal self-tolerance mechanisms.

ABO Blood-Group System↗

PubMed1992

Correlation of antibody multireactivity with variable region primary structure among murine anti-erythrocyte autoantibodies.

A high proportion of the antibodies in the preimmune repertoire bind to several unrelated antigens and are considered to be multireactive. This property is reportedly associated with the antibodies produced by CD5+ B lymphocytes. Because many antibodies specific for bromelain-treated mouse red blood cells (BrMRBC) derive from CD5+ B cells, we tested monoclonal antibodies of this specificity for multireactivity. Two variable region combinations, VH11/V kappa 9 and VH12/V kappa 4, account for greater than 80% of this repertoire, but none of these antibodies exhibited a multireactive phenotype. In contrast, three anti-BrMRBC binding antibodies belonging to the J558 family (BrM1, BrM8, and CH12) showed varying degrees of multireactivity, and bound both highly negatively and positively charged antigens. The amino acid sequences of the VH regions of these antibodies are highly homologous (greater than 85% identical) and they possess large VH-D-J junctions with extensive N-region insertions. The kappa chains of two of these antibodies utilize an identical V kappa gene segment, while the third uses a very different V kappa with only 50% homology. The entire H chain V regions of these antibodies are unusually basic, with isoelectric points of 9.5-10, a feature which might be important in promoting interactions with acidic epitopes. The multireactive antibodies also contain regions with a high concentration of hydroxylside chain amino acids, especially in their VH-D-J junctions. This region also contains acidic amino acid residues, which may be important in binding of positively charged epitopes. We propose that an open, accessible binding site and a charge polarity may be features which facilitate the binding of charged epitopes, providing a structural basis for multireactivity of at least some antibodies.

Amino Acid Sequence↗

PubMed1992

Comparative sensitivities of isolated rat renal arterioles to endothelin.

The specific intrarenal sites and mechanism of endothelin (ET) vascular action are controversial. In this study afferent (AA) and efferent arterioles (EA) were isolated from the kidneys of normal Sprague-Dawley rats. Their respective concentration-dependent changes in lumen diameter in response to ET-1 were compared with those of angiotensin II (ANG II) and norepinephrine (NE). In a second series of experiments, the duration of vasoconstriction to comparable transient submaximal ET-1, ANG II, and NE concentrations in AA and EA was examined. The role of angiotensin II in mediating endothelin vasoconstriction also was examined with the converting-enzyme inhibitor captopril (CAP) and the competitive inhibitor [Sar1,Ala8]ANG II (SAR). The half-maximal constriction concentration (EC50) of ET-1 was less in EA than AA (P < 0.01). EC50 of ET-1 in AA was similar to that of ANG II, but was less than that of NE (P < 0.001). In EA the EC50 of ET-1 was also similar to that of ANG II, but much less than that of NE (P < 0.001). In both AA and EA the duration of ET-1 constriction was at least twice that of ANG II and more than fivefold that of NE. Neither CAP (10(-6) M) nor SAR (10(-7) M) changed the vasoconstrictor response to submaximal concentrations of ET-1 in AA or EA. It is concluded that ET-1 is a potent and prolonged constrictor agonist with a small, but significantly greater, concentration-dependent effect in EA than AA. The constrictor effect of ET-1 does not require ANG II activity.

Angiotensin II↗

PubMed1992

Renal vasculature and ischemic injury.

Functionally similar ischemic acute renal failure (ARF), as estimated by glomerular filtration rates (GFR), was induced by renal artery clamping (RAC) or intrarenal norepinephrine (NE) in rats and renovascular reactivity was examined at 1 week. With RAC-ARF induction there was total renal ischemia followed by abrupt return of renal blood flow (RBF). With NE-ARF induction there was subtotal ischemia (10-15% of basal RBF) with RBF recovery over several hours. Renovascular resistance (RVR) did not change to renal perfusion pressure (RPP) reduction in the autoregulatory range in RAC-ARF but paradoxically increased in NE-ARF. There was an exaggerated response to renal nerve stimulation in NE-ARF but no response in RAC-ARF. There was a vasoconstrictor response to intrarenal norepinephrine in the former but a negligible response in the latter. There was no vasodilation to acetylcholine in either group, but there was a normal response to prostacyclin in NE-ARF. Smooth muscle necrosis was found in 46% of resistance arterial vessels in RAC- but in only 8% of NE-ARF (p less than .001). When mean arterial pressure was reduced to 90 mm Hg for 4 h at 1 week, recurrent azotemia and fresh ischemic injury were noted in NE- but not RAC-ARF. It is concluded that different models of ischemic ARF induction result in different patterns of abnormal postischemic vascular reactivity. Differences in vascular smooth muscle and endothelial injury are due to differences in initial ischemia or rates of postischemic reperfusion.

Acute Kidney Injury↗

PubMed1991

Properties of murine antibodies from different V region families specific for bromelain-treated mouse erythrocytes.

We have analyzed the combining site diversity of murine antibodies reactive with bromelain-treated mouse RBC (BrMRBC) in B10.A mice. Although several VH and V kappa genes are used to generate antibodies of this specificity, two combinations account for more than 80% of the repertoire from the spleen: VH11/V kappa 9 and VH12/V kappa 4. Antibodies representing these two predominant groups were found to correspond to two previously reported distinct cross-reactive Id families accounting for most of the anti-BrMRBC reactivity in several strains of mice. mAb of the VH11/V kappa 9 type bound the haptens trimethyl-ammonium and phosphorylcholine much more avidly (approximately 1000 fold) than did the VH12/V kappa 4 type antibodies. Both of these haptens represent constituents of phosphatidylcholine, which BrMRBC-specific antibodies are reported to bind. Despite this differential reactivity, members of both the VH11/V kappa 9 and VH12/V kappa 4 antibody groups lysed BrMRBC with similar efficiencies. These data suggest that the two major classes of BrMRBC-specific antibodies have at least partially different specificities and imply that the events that lead to their high frequencies in the CD5+ repertoire may result from different selective forces.

Animals↗

PubMed1991

Serial glomerular and tubular dynamics in thyroidectomized rats with remnant kidneys.

Serial measurements were performed in Munich-Wistar rats with five-sixths nephrectomy that had undergone prior selective thyroidectomy (Tx group) or thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal failure progression. At 1 week, inulin clearance rates (Cin) in TxT4 and Tx rats were 0.367 +/- 0.171 and 0.120 +/- 0.036 mL/min, respectively, different at P less than 0.01. Corresponding single-nephron filtration rate (SNGFR), glomerular plasma flow (QA), glomerular transcapillary hydraulic pressure (delta P), and proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats (P less than 0.01). Protein excretion (UPROT) was 151 +/- 40 in TxT4 rats, and 9 +/- 5 mg/d in Tx animals. Glomerular mesangial matrix expansion and focal tubulointerstitial changes were more frequent in TxT4 than Tx rats. By 4 weeks, Cin, SNGFR, QA, glomerular ultrafiltration coefficient (Kf) and Jv were similar in Tx and TxT4. Only glomerular capillary pressure (PGC) remained lower in Tx rats (35 +/- 3 v 50 +/- 3 mm Hg in TxT4, P less than 0.001). UPROT was 161 +/- 24 in TxT4 and 17 +/- 12 mg/d in Tx rats. While 7% +/- 4% of glomeruli showed focal sclerosis in TxT4 rats, there was none in the Tx group. Maximal glomerular planar area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group. However, this measurement was not significantly different between TxT4 and Tx glomeruli at 1 or 4 weeks. Minimal focal tubulointerstitial changes were found in TxT4, but there were not progressive from those observed at 1 week. The reduced PGC at 1 week was the result of a disproportionately greater increase in afferent (RA) than efferent arteriolar resistance (RE) in Tx rats (P less than 0.025); however, at 4 weeks, both RA and RE had decreased to values identical to those in TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean arterial pressure. In conclusion, a reduced PGC was the sole functional correlate of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial nephrectomy model. Suppression of either nephrectomy-related hypertrophy or tubulointerstitial injury by Tx could not be excluded as at least partially protective factors.

Animals↗

PubMed1991

Differences in vascular reactivity in models of ischemic acute renal failure.

To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded.

Acetylcholine↗

PubMed1991

Atrial natriuretic peptide and dopamine in established acute renal failure in the rat.

Recent studies have shown that atrial natriuretic peptide (ANP) alone or combined with dopamine (D) markedly improved renal function when given immediately after an ischemic insult. However, the potential beneficial effect of ANP or ANP-D in the established phase of acute renal failure (ARF) and the duration of this effect have not been examined. In the present study atriopeptin III (APIII) and D, sufficient to maintain mean arterial pressure between 100 and 110 mm Hg, or normal saline were given i.v. for four hours to awake Munich-Wistar rats (N = 6 each group) two days after ARF induction with intrarenal norepinephrine (NE). Renal function and morphology were then examined two days after treatment (Day 4). Serum creatinine (SCr) was similarly increased in both groups at the time of APIII-D or saline infusion (Day 2). By Day 4 SCr had decreased to the pre-ARF induction level in APIII-D-treated rats (P less than 0.005), but continued to rise in saline-treated animals (P less than 0.025). Day 4 renal blood flow and glomerular filtration rate (GFR) were higher in APIII-D-compared to the saline-treated group (9.13 +/- 1.14 vs. 4.41 +/- 2.25 ml/min and 0.787 +/- 0.066 vs. 0.370 +/- 0.185 ml/min, respectively, both P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1991

Effects of atriopeptin III on isolated rat afferent and efferent arterioles.

The effects of atriopeptin III (AP III) on in vitro prepared afferent (AA) and efferent arterioles (EA) from rat kidneys were tested in a system in which lumen diameter could be measured. AP III (10(-13)-10(-7) M) had no effect on lumen diameter of AA that were not preconstricted. When AA were preconstricted with either angiotensin II (ANG II) or norepinephrine (NE), however, AP III increased lumen diameter in a concentration-dependent manner to the preconstriction baseline value. Maximal vasodilation occurred at 10(-10) M AP III. Unlike AA, EA constricted by 50% to 10(-10) M AP III further constricted EA that were pretreated with ANG II or NE. Dilation in ANG II-preconstricted AA to AP III was not inhibited by indomethacin. Constriction of EA to AP III was not altered by [Sar1-Ala8] ANG II, enalapril, OKY 046, or phentolamine. Results indicate that in isolated renal arterioles AP III dilates preconstricted AA but constricts EA that have either not been pretreated or have been preconstricted with other agonists. The effect of AP III on preconstricted AA does not require vasodilator prostaglandin mediation. The constrictor effect of AP III on EA is not dependent on angiotensin, thromboxane, or alpha-adrenergic mediation.

Angiotensin II↗

PubMed1991

Direct studies on the control of the renal microcirculation.

Recent advances in videomicroscopy combined with the development of several innovative in vivo and in vitro preparations now allow for direct study of the renal microcirculation. Blood flow in vasa recta capillaries of the rat can be studied by using video-microscopy, and changes in the flow of red blood cells in the renal cortex and papilla can be continuously monitored by using laser-Doppler flowmetry. All elements of the renal microcirculation can be visualized with the in vitro perfused juxtamedullary nephron or hydronephrotic kidney preparations. Pressures, blood flows, and vascular diameters in individual vessels can be directly measured in these preparations. Renal arterioles can be microdissected from the kidneys of several species and cannulated and pressurized in vitro for the study of pressure-diameter relationships and vascular responses to different agonists. In addition, membrane potentials and intracellular ion concentrations can now be measured in isolated renal arterioles by using microelectrodes and fluorescence microscopy. Thus, it is possible to study the control of renal vascular tone at all levels of integration from signal transduction in isolated cells to direct analysis of the regulation of hemodynamics in different regions of the microcirculation of the kidney in intact animals.

Animals↗