Biomedical subjects

L G Navar

Publications and source records attributed to L G Navar.

At least 19 recordsLinked to original sources

PubMed1998

Renal uptake of circulating angiotensin II in Val5-angiotensin II infused rats is mediated by AT1 receptor.

Previous studies have demonstrated that augmentation of intrarenal angiotensin II (ANG II) levels during ANG II induced hypertension involves both endogenous formation and accumulation of circulating ANG II. The present work extends these findings and determines whether accumulation of infused ANG II in the kidney requires AT1 receptor activation by using Val5-ANG II as the infused peptide. Male Sprague-Dawley rats were uninephrectomized and divided into three groups: control (n = 6), Val5-ANG II (exogenous form) infused (n = 8), and Val5-ANG II infused rats treated with losartan (n = 8). Val5-ANG II, which has the same biological and immunoreactive properties as endogenous ANG II, was infused at 40 ng/min via an osmotic minipump implanted subcutaneously. By day 12, systolic blood pressure (SBP) increased significantly in Val5-ANG II infused rats (197 +/- 7 mm Hg). As previously shown, the development of hypertension in ANG II infused rats was prevented by losartan treatment. Blood and kidney samples were harvested, subjected to HPLC to separate Val5-ANG II (exogenous) from Ile5-ANG II (endogenous) and the fractions were measured by radioimmunoassay. In the Val5-ANG II infused rats treated with losartan, total plasma ANG II levels were elevated to a greater extent than in rats not treated with losartan (289 +/- 20 v 119 +/- 14 fmol/mL). However, losartan markedly decreased by 88% the enhancement of intrarenal Val5-ANG II content that occurred in the rats infused with Val5-ANG II alone. These results demonstrate that AT1 receptor blockade markedly reduces the intrarenal uptake of circulating ANG II that occurs in ANG II induced hypertension.

Angiotensin I↗

PubMed1998

Heterogeneous activation mechanisms in the renal microvasculature.

Vascular smooth muscle cells in different renal microvascular segments utilize different activation mechanisms to respond to mechanical and vasoactive stimuli. L-type Ca2+ channel blockers vasodilate primarily the preglomerular vascular resistance component responsible for autoregulation. Local interstitial infiltration of Ca2+ channel blockers increases glomerular pressure and markedly reduces vascular responsiveness of the tubuloglomerular feedback mechanism. Ca2+ channel blockers selectively attenuate the afferent vasoconstrictor responses to increases in perfusion pressure. Although both afferent and efferent arterioles constrict in response to angiotensin II (Ang II), afferent but not efferent constriction requires Ca2+ influx through L-type Ca2+ channels. Sensitivity of the preglomerular arterioles to Ang II is also heterogeneous with the greatest sensitivity in glomerulus-near, terminal segments. Adenosine triphosphate (ATP) is a vasoconstrictor agonist that selectively activates Ca2+ entry pathways in afferent arterioles but has no effect on efferent arterioles. In isolated preglomerular smooth muscle cells, increasing extracellular [KCl] increases intracellular Ca2+ by stimulating voltage-dependent Ca2+ influx. Ang II, norepinephrine, and ATP also elicit similar increases in intracellular Ca2+. Mechanical and agonist-induced voltage-dependent Ca2+ influx is thus a primary pathway in the control of cytosolic Ca2+ in afferent arterioles. Efferent arterioles, however, rely primarily on intracellular Ca2+ mobilization and other Ca2+ influx pathways.

Animals↗

PubMed1998

Integrating multiple paracrine regulators of renal microvascular dynamics.

There has been tremendous growth in our knowledge about the multiple interacting mechanisms that regulate renal microvascular function. Paracrine signals originating from endothelial and epithelial cells exert profound influences on the basal tone and reactivity of the pre- and postglomerular arterioles. Selective responsiveness of these arterioles to various stimuli is possible because of differential activating mechanisms in vascular smooth muscle cells of afferent and efferent arterioles. Afferent arterioles rely predominantly on voltage-dependent calcium channels, while efferent arterioles utilize other mechanisms for calcium entry as well as intracellular calcium mobilization. The autoregulatory responses of preglomerular arterioles exemplify the selectivity of these complex control mechanisms. The myogenic mechanism responds to increases in renal perfusion pressure through "stretch-activated" cation channels that lead to depolarization, calcium entry, and vascular contraction. Autoregulatory efficiency is enhanced by the tubuloglomerular feedback (TGF) mechanism which responds to flow-dependent changes in tubular fluid composition at the level of the macula densa and transmits signals to the afferent arterioles to alter the activation state of voltage-dependent calcium channels. Recent studies have implicated extracellular ATP as one paracrine factor mediating TGF and autoregulatory related signals to the afferent arterioles. Other paracrine agents including nitric oxide, angiotensin II, adenosine, and arachidonic acid metabolites modulate vascular responsiveness in order to maintain an optimal balance between the metabolically determined reabsorptive capabilities of the tubules and the hemodynamically dependent filtered load.

Animals↗

PubMed1998

Neuronal nitric oxide synthase modulates rat renal microvascular function.

This study was performed to determine the influence of neuronal nitric oxide synthase (nNOS) on renal arteriolar tone under conditions of normal, interrupted, and increased volume delivery to the macula densa segment and on the microvascular responses to angiotensin II (ANG II). Experiments were performed in vitro on afferent (21.2 +/- 0.2 microns) and efferent (18.5 +/- 0.2 microns) arterioles of kidneys harvested from male Sprague-Dawley rats, using the blood-perfused juxtamedullary nephron technique. Superfusion with the specific nNOS inhibitor, S-methyl-L-thiocitrulline (L-SMTC), decreased afferent and efferent arteriolar diameters, and these decreases in arteriolar diameters were prevented by interruption of distal volume delivery by papillectomy. When 10 mM acetazolamide was added to the blood perfusate to increase volume delivery to the macula densa segment, afferent arteriolar vasoconstrictor responses to L-SMTC were enhanced, but this effect was again completely prevented after papillectomy. In contrast, the arteriolar diameter responses to the nonselective NOS inhibitor, N omega-nitro-L-arginine (L-NNA) were only attenuated by papillectomy. L-SMTC (10 microM) enhanced the efferent arteriolar vasoconstrictor response to ANG II but did not alter the afferent arteriolar vasoconstrictor responsiveness to ANG II. In contrast, L-NNA (100 microM) enhanced both afferent and efferent arteriolar vasoconstrictor responses to ANG II. These results indicate that the modulating influence of nNOS on afferent arteriolar tone of juxtamedullary nephrons is dependent on distal tubular fluid flow. Furthermore, nNOS exerts a differential modulatory action on the juxtamedullary micro-vasculature by enhancing efferent, but not afferent, arteriolar responsiveness to ANG II.

Acetazolamide↗

PubMed1998

Renoprotective effects of nitric oxide in angiotensin II-induced hypertension in the rat.

Experiments were performed in anesthetized male Sprague-Dawley rats to determine whether increased nitric oxide (NO) activity during the development of hypertension exerts a protective effect on renal cortical blood flow (CBF) and medullary blood flow (MBF). The effects of acute NO synthase inhibition on renal function and on CBF and MBF, measured by laser-Doppler flow probes, were evaluated in control and ANG II-infused hypertensive rats, prepared by the infusion of ANG II at a rate of 65 ng/min via osmotic minipumps implanted subcutaneously for 13 days. In normotensive rats (n = 8), intravenous infusion of N omega-nitro-L-arginine (NLA; 20 micrograms.100 g-1.min-1) decreased CBF by 21 +/- 4% and MBF by 49 +/- 8% and increased blood pressure from 118 +/- 1 to 140 +/- 2 mmHg. In ANG II-infused rats (n = 7), CBF and MBF decreased by 46 +/- 5% and 25 +/- 6%, respectively, during infusion of NLA. Arterial pressure increased from 160 +/- 5 to 197 +/- 7 mmHg, which was a greater absolute increase than in normotensive controls. Basal renal blood flow (RBF), estimated from p-aminohippurate clearance and hematocrit, was similar in both the control (6.0 +/- 0.5 ml.min-1.g-1) and hypertensive (6.0 +/- 0.6 ml.min-1.g-1) rats. However, NLA-induced reductions in RBF averaged 60 +/- 5% in the hypertensive rats, compared with 31 +/- 9% observed in control rats. GFR in control (0.97 +/- 0.03 ml.min-1.g-1) and hypertensive rats (0.78 +/- 0.12 ml.min-1.g-1) decreased to a similar extent during the first 30-min period of NLA infusion. GFR returned toward control levels in control rats; in contrast, GFR remained significantly decreased in the ANG II-infused rats (0.58 +/- 0.11 ml.min-1.g-1). Basal urinary sodium excretion (0.2 +/- 0.08 mueq.min-1.g-1), fractional excretion of sodium (0.3 +/- 0.13%), and urine flow (4.9 +/- 0.39 microliters.min-1.g-1) in hypertensive rats did not increase significantly after NLA treatment as occurred in normotensive controls. These data suggest that a compensatory increase in nitric oxide activity partially counteracts the vasoconstrictor influence of elevated ANG II levels to regulate renal hemodynamics and maintain cortical perfusion in the renal circulation.

Angiotensin II↗

PubMed1998

Effects of acute AT1 receptor blockade by candesartan on arterial pressure and renal function in rats.

Experiments were performed on normal anesthetized rats to determine the effects of candesartan, a novel AT1 receptor antagonist, on the arterial pressure and renal hemodynamic responses to bolus doses of angiotensin II (ANG II) and on renal hemodynamics and sodium excretion. Control arterial pressure responses to bolus ANG II doses of 10, 50, 100 and 1,000 ng were 26 +/- 6, 54 +/- 7, 57 +/- 7, and 79 +/- 7 mmHg; the decreases in cortical renal blood flow (CRBF), measured with laser-Doppler flowmetry, were 47 +/- 9, 64 +/- 8, 71 +/- 6, and 82 +/- 6%. The vasoconstrictor responses to ANG II up to 1,000 ng were completely blocked by candesartan doses of 1 and 0.1 mg/kg, whereas treatment with 0.01 mg/kg candesartan attenuated the arterial pressure and CRBF responses. The higher doses of candesartan (1 and 0.1 mg/kg) elicited rapid decreases in arterial pressure, leading to associated decreases in sodium excretion. Renal blood flow (RBF), glomerular filtration rate (GFR), and urine flow also decreased following treatment with candesartan at 1 mg/kg. In contrast, when candesartan was given at 0.01 mg/kg, which did not decrease arterial pressure significantly, there were significant increases in GFR (16 +/- 4), RBF (9 +/- 2), urine flow (11 +/- 2), sodium excretion (35 +/- 7), and fractional sodium excretion (39 +/- 8%). The inability to overcome blockade, even with very high ANG II doses, indicates that candesartan is a potent noncompetitive blocker of ANG II pressor and renal vasoconstrictor effects. The lower candesartan dose that did not cause significant hypotension elicited substantial increases in RBF, GFR, and sodium excretion, revealing the direct renal vasodilator and natriuretic effects of AT1 receptor blockade.

Angiotensin II↗

PubMed1998

Cyclooxygenase-2 participates in tubular flow-dependent afferent arteriolar tone: interaction with neuronal NOS.

To delineate the microvascular role of cyclooxygenase-2 (Cox-2) in modulating tubuloglomerular feedback (TGF) signals and to determine its relationship to neuronal nitric oxide synthase (nNOS), afferent (AA) and efferent (EA) arteriolar diameters of rat kidneys were assessed using the blood-perfused juxtamedullary nephron technique. The Cox-2 inhibitor NS-398 (10 microM) did not alter AA diameters in untreated kidneys but significantly constricted AAs by 17.0 +/- 2.2% in kidneys treated with 10 mM acetazolamide, which enhances TGF-mediated AA constriction by increasing distal volume delivery. The NS-398-induced AA constriction was prevented after interruption of distal delivery by transection of the loops of Henle. The effect was selective for AAs since NS-398 did not influence EAs of untreated or acetazolamide-treated kidneys. Pretreatment with the nNOS inhibitor S-methyl-L-thiocitrulline (10 microM) prevented the NS-398-induced AA constriction observed during acetazolamide treatment. Although we previously demonstrated that acetazolamide treatment enhanced AA constrictor response to S-methyl-L-thiocitrulline, the enhancement by acetazolamide was inhibited by pretreatment with 10 microM NS-398 (16.4 +/- 1.9 and 15. 0 +/- 0.5% with and without acetazolamide, respectively, P > 0.05). These results indicate that, during increased activation of TGF-dependent vasoconstrictor signals, Cox-2 generates vasodilatory metabolites in response to increased nNOS activity and thus participates in the counteracting modulation of TGF-mediated AA constriction.

Acetazolamide↗

PubMed1998

Interactive nitric oxide-angiotensin II influences on renal microcirculation in angiotensin II-induced hypertension.

The present study was conducted to determine the contribution of nitric oxide to angiotensin II (Ang II) reactivity of afferent and efferent arterioles from Ang II-infused hypertensive rats. Experiments were performed in vitro with the blood-perfused juxtamedullary nephron technique in kidneys harvested from hypertensive Sprague-Dawley rats (181+/-1 mm Hg) that had received 60 ng/min Ang II subcutaneously for 13 days. Superfusion with 0.1, 1, and 10 nmol/L Ang II reduced afferent arteriolar diameter (18.1+/-0.6 microm; n=12) by 10.0+/-0.7%, 28.1+/-1.7%, and 52.8+/-1.9%, respectively, and efferent arteriolar diameter (17.2+/-1.4 microm; n=8) decreased by 9.3+/-0.7%, 27.0+/-1.2%, and 50.4+/-1.6%, respectively. Nitric oxide synthase inhibition with 100 micromol/L N(omega)-nitro-L-arginine (NLA) reduced resting afferent and efferent arteriolar diameters to 14.7+/-0.4 and 14.3+/-1.2 microm, respectively, and enhanced afferent but not efferent arteriolar reactivity to Ang II. The enhanced afferent arteriolar reactivity to Ang II was eliminated by addition of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP, 10 micromol/L), which reversed the NLA-induced decrease in diameter. Addition of 10 micromol/L SNAP, without NLA, blunted efferent but not afferent arteriolar reactivity to Ang II. Afferent (n=7) and efferent arteriolar diameters (n=6) decreased by 48.5+/-2.2% and 41.0+/-1.9%, respectively, in response to 10 nmol/L Ang II. These results suggest that in this model of hypertension, maintained nitric oxide production in afferent arterioles counteracts the enhanced afferent arteriolar reactivity that occurs in Ang II-induced hypertension.

Angiotensin II↗

PubMed1998

Intrarenal nitric oxide activity and pressure natriuresis in anesthetized dogs.

Recent studies have indicated that changes in intrarenal nitric oxide (NO) production participate in mediating arterial pressure-induced changes in urinary sodium excretion. Until recently, however, the means to measure changes in intrarenal NO activity in vivo have not been available. For the present study, changes in renal tissue NO activities were assessed directly using an NO-selective microelectrode inserted into the cortical tissue of anesthetized dogs. Control studies demonstrated that the electrode was responsive to intrarenal bolus injections of acetylcholine and to the NO donor S-nitroso-acetylpenicillamine (SNAP). Intrarenal nitro-L-arginine (50 microg x kg(-1) x min(-1)) decreased renal tissue NO concentration by 593+/-127 nmol/L (P<0.05; n=7). Infusions of SNAP (1, 2, and 3 microg x kg(-1) x min(-1) for 25 minutes) in nitro-L-arginine-treated dogs (n=5) resulted in dose-dependent increases in renal tissue NO activity, which showed a positive correlation with changes in urinary excretion rates of NO metabolites, nitrates and nitrites, (r=0.62, P<0.05) and sodium (r=0.78, P<0.01). During graded reductions of renal arterial pressure within the autoregulatory range (144+/-3 to 73+/-2 mm Hg; n=10), there were decreases in tissue NO activity that were positively correlated with changes in renal arterial pressure (r=0.45; P<0.05), urinary nitrate/nitrite excretion (r=0.64, P<0.005), and urinary sodium excretion (r=0.46; P<0.05). These data support the hypothesis that acute changes in renal arterial pressure result in alterations in intrarenal NO activity, which may be responsible for the associated changes in sodium excretion.

Animals↗

PubMed1997

Animal rights.

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Animal Rights↗

PubMed1997

The kidney in blood pressure regulation and development of hypertension.

Systemic arterial pressure is a dynamic and responsive physiologic parameter that can be influenced by many different factors. In particular, short-term changes in arterial pressure are caused by a myriad of mechanisms that affect cardiac output, total peripheral resistance, and cardiovascular capacitance. In the long run, however, most of these actions can be buffered or compensated by appropriate renal adjustments of sodium balance, ECFV, and blood volume. As long as the mechanisms regulating sodium excretion can maintain sodium balance by appropriately modulating the sensitivity of the pressure-natriuresis relationship, normal arterial pressure can be sustained. Derangements that compromise the ability of the kidneys to maintain sodium balance, however, can result in the kidney's need for an elevated arterial pressure to reestablish net salt and water balance.

Blood Pressure↗

PubMed1997

Plasma renin activity and metabolic clearance rate of angiotensin II in the unstressed aging rat.

We conducted studies in conscious chronically catheterized, trained young (3-5 months) and old (18-20 months) rats to assess the impact of aging on baseline renin activity (PRA) and metabolic clearance rate (MCR) of angiotensin II (ANG II). We observed that under unstressed conditions the baseline values of PRA and plasma ANG II were no different in young versus old rats (1.8 +/- 0.2 versus 1.5 +/- 0.2 ng Al/ml/h and 18 +/- 3 versus 15 +/- 2 fmol/ml, respectively). Values of PRA in the present study were similar to those reported by others for old rats, but our young rat values were lower than usually reported. This probably reflects our use of an unstressed preparation. We also observed a blunted increase in PRA in old rats in response to acute converting enzyme inhibition. Overall, our observations suggest that old rats may lose their ability to increase PRA in response to acute stimuli, including perhaps, the stress of blood drawing in emotionally or surgically stressed preparations. We also observed that the MCR of ANG II increased with age, despite similar baseline plasma ANG II concentrations in young and old. This suggests that with aging, an increase occurs in the rate of synthesis of ANG II. These results emphasize the importance of establishing true baseline values for indices of the renin-ANG II system in aging.

Aging↗

PubMed1997

Nitric oxide in the mediation of pressure natriuresis.

1. Recent studies have indicated that nitric oxide (NO) production in the kidney contributes to the regulation of renal haemodynamics and excretory function. Inhibition of nitric oxide synthase (NOS) reduces renal blood flow by approximately 25% and markedly reduces sodium excretion without reductions in filtered load. In particular, inhibition of NO synthesis markedly suppresses the slope of the arterial pressure-mediated response in sodium excretion. 2. Further studies have shown that constant intrarenal infusion of a NO donor in dogs treated with a NOS inhibitor produced diuretic and natriuretic responses but failed to restore the slope of the pressure-induced natriuretic response. These data indicate that an alteration in intrarenal NO activity, rather than the simple presence of NO during changes in arterial pressure is required for full expression of pressure natriuretic responses. 3. In support of the hypothesis that NO is involved in the mediation of pressure natriuresis, we also recently demonstrated a direct relationship between changes in arterial pressure and urinary excretion rate of sodium as well as nitrate and nitrite (a marker for endogenous NO activity) in the presence of efficient autoregulation of cortical and medullary blood flow. 4. The direct inhibitory actions of NO on tubular sodium reabsorption have also been observed in cultured tubular cells as well as isolated, perfused cortical collecting duct segments. 5. Thus, the collective data suggest that acute changes in arterial pressure induce changes in intrarenal NO production, which may directly alter tubular reabsorptive function to manifest the phenomenon of pressure natriuresis.

Animals↗

PubMed1997

Immunohistochemical localization of ANG II AT1 receptor in adult rat kidney using a monoclonal antibody.

Molecular and functional studies have suggested that AT1 receptors are present in most nephron segments, yet direct demonstration of AT1 at these sites is lacking. The present study was performed to determine the intrarenal localization of the AT1 receptor utilizing a monoclonal anti-peptide (amino acid residues 8-17) antibody (6313/G2) in adult male Sprague-Dawley rats. Western blot analysis of kidney protein extracts showed a predominant 41-kDa immunoreactive band corresponding to the molecular weight of the deduced cDNA sequence. To determine optimal fixation conditions, kidney tissues were immersion fixed in Bouin's solution, 10% buffered Formalin, or 4% paraformaldehyde. Specificity of immunostaining was documented by preadsorption of the antibody with the immunogenic peptide sequence. Prominent AT1 immunostaining was visualized in the proximal tubule brush-border and basolateral membranes. In addition, distal tubules, cortical and medullary collecting ducts, and the renal arterial vasculature exhibited specific immunoreactivity. Glomerular staining for AT1 was observed in mesangial cells and podocytes. Macula densa cells stained positively. Similar localization of the AT1 receptor was obtained using the three tissue fixation methods, although the intensity of vascular and glomerular staining was highest in Bouin-fixed tissues. The present study demonstrates that the AT1 receptor is more widely distributed along the nephron than previously described and includes renal vascular smooth muscle and proximal and distal epithelial sites.

Amino Acid Sequence↗

PubMed1997

Role of renal nerves in afferent arteriolar reactivity in angiotensin-induced hypertension.

The objective of this study was to determine the contribution of renal nerves to the enhanced afferent arteriolar reactivity observed in angiotensin II (Ang II)-induced hypertension. Uninephrectomized Sprague-Dawley rats were divided into four groups: sham rats, renal-denervated rats, Ang II-infused (at 40 ng/min for 13 days) rats, and Ang II-infused+renal-denervated rats. With the use of an implanted arterial catheter, mean arterial pressure (MAP) was monitored in conscious rats. Ang II infusion resulted in a progressive increase in MAP from 98 +/- 1 (day 0) to 166 +/- 7 mm Hg (day 13). This increase in MAP was attenuated in denervated rats and averaged 136 +/- 3 mm Hg on day 13. Kidneys were harvested on day 13 for microcirculatory experiments or measurement of intrarenal Ang II levels. Basal afferent arteriolar diameter was similar in all groups, and group averages ranged from 19.6 to 20.7 microns. Chronic Ang II infusion increased intrarenal Ang II levels. Renal denervation did not alter this effect. Increasing perfusion pressure from 100 to 160 mm Hg reduced afferent arteriolar diameter significantly by 11.2 +/- 0.6% in the sham group and by a similar degree in the remaining three groups. Superfusion with Ang II (10 nmol/L) reduced afferent arteriolar diameter by 34.3 +/- 2.0% in the sham group. This response was enhanced in Ang II-infused (62.3 +/- 3.4%) but not in renal-denervated or Ang II-infused+renal-denervated rats. Additionally, the enhanced afferent arteriolar reactivity to Ang II was not influenced by adrenergic receptor blockade. The afferent arteriolar response to norepinephrine was enhanced in renal-denervated, Ang II-infused, and Ang II-infused+renal-denervated rats compared with sham controls. Administration of the calcium ionophore A23187 decreased afferent arteriolar diameter similarly in all four groups. These results indicate that renal nerves contribute to the development of hypertension and to the enhanced afferent arteriolar responsiveness to Ang II elicited by chronic Ang II infusion.

Angiotensin II↗

PubMed1997

Pressure natriuresis and renal medullary blood flow in dogs.

In the present study, we evaluated the effects of changes in arterial pressure on regional renal blood flows and sodium excretion in anesthetized dogs during control conditions and after 5% volume expansion with isotonic saline. Medullary and cortical blood flow responses were determined with laser-Doppler needle flow probes inserted into the midmedullary and midcortical regions, and whole-kidney blood flow was assessed with an electromagnetic flow probe. Volume expansion in six dogs caused marked increases in urine flow (20.2 +/- 5.5 to 82.5 +/- 22.7 microL.min-1.g-1) and sodium excretion (3.2 +/- 0.5 to 11.1 +/- 2.7 mumol.min-1.g-1), with slight increases in glomerular filtration rate (0.92 +/- 0.03 to 1.01 +/- 0.02 mL.min-1.g-1) but no significant changes in total renal blood flow (4.7 +/- 0.3 to 5.2 +/- 0.6 mL.min-1.g-1), medullary blood flow (+6 +/- 9%), or cortical blood flow (+12 +/- 10%). During stepwise reductions in renal arterial pressure (150 to 75 mm Hg) elicited with a renal arterial occluder, both before and after volume expansion, medullary, cortical, and total renal blood flows as well as glomerular filtration rate exhibited efficient autoregulation, with slopes not significantly different from zero over this range of arterial pressure. Ther were marked increases in the slopes of the relationships between arterial pressure and urine flow (0.18 +/- 0.05 to 0.78 +/- 0.27 microL.min-1.g-1.mm Hg-1) as well as sodium excretion (0.03 +/- 0.004 to 0.10 +/- 0.03 mumol.min-1.g-1.mm Hg-1) during volume expansion. These data demonstrate that medullary blood flow is efficiently autoregulated in dogs during control and volume-expanded states and indicate that the mechanism responsible for the arterial pressure-induced changes in sodium excretion does not depend on coincident alterations in medullary blood flow.

Animals↗

PubMed1997

Cardiovascular research support by the American Heart Association in Louisiana.

The American Heart Association (AHA) was founded in 1924 by a group of physician-scientists to promote the exchange of research ideas in an era when the treatment of heart disease was extremely frustrating. The organization has evolved to include education and community service in its mission, but the support and promotion of quality research has remained at the AHA's core. Research support by the AHA has been responsible for major advances in cardiovascular medicine, including the development of diuretics, pacemakers, artificial heart valves, defibrillators, cardiopulmonary resuscitation, hypercholesterolemia therapy, and artificial surfactant. Working to ensure the efficient distribution of funds, the AHA has distributed nearly $1.4 billion in support of quality research for graduate and medical students, post-doctoral fellows, and beginning and established investigators. Such support has assisted in the career development of four Nobel Prize winners. While cardiovascular disease remains America's leading cause of death, the activities of the AHA continue to support advances in its diagnosis and treatment.

American Heart Association↗

PubMed1997

Intrarenal production of angiotensin II.

The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal hemodynamics and tubular transport function. Much of the intrarenal angiotensin II (ANG II) is formed locally as evidenced by intrarenal ANG II contents that are much greater than can be explained from the circulating ANG II concentration. Intrarenal ANG II is formed from systemically delivered ANG I and from intrarenally formed ANG I derived from systemically delivered angiotensinogen as well as locally synthesized angiotensionogen. There is a regional distribution of intrarenal ANG II in that the medullary content per gram of tissue is four to five times higher than the cortical content. In addition, most of the cortical ANG II is compartmentalized in the renal interstitial fluid and in the tubular fluid. Proximal tubule cells contain all the components of the renin-angiotensin system necessary for synthesis and secretion of ANG II. Proximal tubule concentrations of ANG II as well as ANG I and angiotensinogen support the concept that the proximal tubule cells secrete ANG II or precursors of ANG II into the tubular fluid. The intratubular concentrations of ANG II are in the nanomolar range, indicating a substantial capability to influence luminal ANG II receptors on the tubule cell membranes. Thus, much of the ANG II-dependent actions on tubular transport functions could be due to specific effects of locally synthesized ANG II on luminal ANG II receptors. Experimental evidence shows that the intratubular ANG II concentrations are regulated independently of the circulating concentrations, but the specific mechanisms responsible remain to be delineated.

Angiotensin I↗