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Biomedical subjects

L G Navar

Publications and source records attributed to L G Navar.

At least 163 records · Page 9Linked to original sources
PubMed1985

Tubular transport responses to angiotensin.

Angiotensin II (ANG II) is a powerful effector agent in the regulation of extracellular volume and exerts an important influence on renal sodium excretion. In addition to its effects on aldosterone secretion, ANG II acts directly on the kidney causing retention of sodium at low (physiological) doses and enhanced sodium excretion at high doses. The mechanism for these responses involves vasoconstrictor actions of ANG II on the renal vasculature and a direct action of the peptide on tubular reabsorption. Micropuncture and microperfusion studies have demonstrated that proximal tubular sodium and water transport are stimulated by physiological concentrations (10(-12) to 10(-10) M) of ANG II on the peritubular side, whereas higher doses (10(-7) M) cause inhibition. A luminal site of action in the proximal tubule has also been reported and additional more distal sites are indicated. [125I]ANG II binding sites on the brush border and basolateral membranes of proximal tubule cells have high affinity (Kd in the nanomolar range) for ANG II and lower affinity for ANG III. The biphasic action of ANG II is exerted directly on the epithelial cells and appears to be electroneutral. The data indicate that ANG II binds to receptors on the basolateral cell membrane and alters the rate of entry of sodium through the luminal membrane to increase or decrease, depending on the concentration of peptide. Several possible cellular mechanisms that could mediate these responses are discussed.

Angiotensin II↗
PubMed1984

Effects of renal arterial angiotensin I infusion on glomerular dynamics in sodium replete dogs.

During intrarenal infusion of angiotensin I (AI), conversion to angiotensin II (AII) within the kidney has been shown to occur early enough to decrease glomerular filtration rate (GFR). To evaluate further the mechanism by which AI decreases GFR, micropuncture studies were conducted in sodium replete dogs. Feedback-mediated alterations in glomerular function were minimized by reducing renal arterial pressure to 90 mm Hg. During infusion of AI (0.82 +/- 0.01 micrograms min-1), renal blood flow (3.91 +/- 0.25 ml min-1 g-1) and GFR (0.63 +/- 0.04 ml min-1 g-1) decreased by 36.7 +/- 6.1% and 18.9 +/- 6.1%, respectively. Similarly, single nephron GFR decreased from 66.4 +/- 3.8 to 40.0 +/- 3.2 nl min-1 and estimated glomerular plasma flow (280 +/- 49 nl min-1) decreased by 55 +/- 6%. Stop-flow pressure (40.5 +/- 3.6 mm Hg) did not change significantly, while proximal tubular (21.8 +/- 1.4 mm Hg) and peritubular capillary pressures (13.2 +/- 1.8 mm Hg) decreased by 25.5 +/- 2.8% and 49.4% +/- 5.1%, respectively. Glomerular capillary and effective filtration pressures were not altered significantly. There were increases in both preglomerular (168%) and efferent (203%) arteriolar resistances, along with a decrease in the glomerular filtration coefficient (Kf) from 4.6 +/- 0.6 to 2.5 +/- 0.5 nl mm Hg-1 min-1. These data indicate that augmented intrarenal conversion of circulating AI reduces GFR as a consequence of decreases in Kf as well as in glomerular plasma flow, the latter being due to concomitant increases in preglomerular and efferent arteriolar resistances.

Angiotensin I↗
PubMed1984

Evidence for angiotensin-stimulated proximal tubular fluid reabsorption in normotensive and hypertensive rats: effect of acute administration of captopril.

The effects of captopril on mean arterial blood pressure and proximal tubular fluid reabsorption (JV) were examined in anaesthetized normotensive rats and in the non-clipped kidneys of two-kidney, one-clip Goldblatt hypertensive rats. In the normotensive animals, captopril reduced arterial blood pressure from 121 +/- SD 9 to 106 +/- 10 mmHg and JV decreased from 3.78 +/- 0.45 to 2.57 +/- 0.58 X 10(-4) mm3 mm-2 s-1. Captopril had a greater effect on blood pressure in the hypertensive animals (172 +/- 17 reduced to 133 +/- 23 mmHg) although the decrease in JV from 3.62 +/- 0.12 to 2.40 +/- 0.40 was similar to that observed in normotensive animals. These results provide evidence that, in the anaesthetized rat, angiotensin II contributes to the maintenance of the rate of proximal fluid reabsorption. The magnitude of the angiotensin-stimulated component of proximal fluid absorption is similar in normotensive and two-kidney, one-clip Goldblatt hypertensive rats.

Absorption↗
PubMed1984

In vitro perfusion of juxtamedullary nephrons in rats.

Anatomical studies of rat kidneys revealed the presence of a unique population of juxtamedullary glomeruli (JMG) located at the inside cortical surface apposed to the pelvic lining and arcuate veins. These "superficial" JMG were exposed by longitudinally bisecting the kidney, reflecting the papilla, removing the pelvic mucosa, and transecting the venous walls. A microperfusion system was developed to allow blood perfusion of these nephrons via arcuate arteries. At a perfusion pressure of 100 mmHg, with most of the preglomerular pressure drop being localized to the terminal afferent arteriolar segment. In subsequent studies, blood hematocrit was reduced to approximately 30% with physiological solutions devoid of or containing albumin, and rats were treated with a converting enzyme inhibitor. In these conditions, single nephron glomerular filtration rate averaged 34 +/- 4 nl/min (low plasma colloid osmotic pressure, PCOP) and 23.3 nl/min (maintained PCOP). Proximal tubule reabsorption ranged from 17 to 29%. In conclusion, the integrity of nephron function is maintained in this model, which may provide further insights into the dynamics of filtration and reabsorption processes of juxtamedullary nephrons.

Absorption↗
PubMed1984

Tubuloglomerular feedback-mediated decreases in glomerular pressure in Munich-Wistar rats.

These experiments were performed to evaluate directly measured glomerular capillary pressure and single nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses in Munich-Wistar rats during increased distal flow rate achieved by infusing an isotonic electrolyte solution into unblocked late proximal tubules. Arterial pressure averaged 114 +/- 2 mmHg and proximal tubule pressure was 14 +/- 1 mmHg. In eight tubules, control SNGFR based on distal tubular fluid collections averaged 22 +/- 3 nl/min, decreased to 15 +/- 2.3 nl/min when 10-12 nl/min of perfusate was infused into the late proximal tubule, and further decreased to 9 +/- 1.7 nl/min at an infusion of 20-24 nl/min. In 22 tubules, control glomerular capillary pressure was 55 +/- 1.6 mmHg, decreased to 43 +/- 2.5 mmHg with addition of perfusate into a late proximal tubule at a rate of 24 nl/min, and returned to 53 +/- 3.1 mmHg when perfusion was stopped. In eight nephrons, glomerular capillary pressure was shown to be responsive to smaller increments in the late proximal infusion rate and was reduced by 4 +/- 0.5 and 7 +/- 1.1 mmHg at the intermediate rates of 10 and 15 nl/min, respectively. These results demonstrate that glomerular pressure decreases during increased distal delivery even when the tubule is not blocked. They are consistent with the hypothesis that increases in afferent arteriolar resistance are primarily responsible for feedback-mediated reductions in glomerular filtration rate.

Animals↗
PubMed1983

Glomerular filtration dynamics during renal vasodilation with acetylcholine in the dog.

The reason for the failure of glomerular filtration rate (GFR) to exhibit plasma flow dependency during pharmacologic vasodilation remains unclear although it has been suggested on the basis of experiments in rats that vasodilators may lead to a reduction in the glomerular filtration coefficient (Kf). To evaluate the applicability of this hypothesis to the dog, the effects of vasodilation with acetylcholine on glomerular dynamics and Kf were evaluated in two groups of dogs. One group (n = 19) was studied at spontaneous arterial pressures to allow maximum vasodilation to occur. In the other group (n = 5), renal arterial pressure was reduced and maintained at approximately 89 mmHg. Glomerular filtration rate and single nephron glomerular filtration rate were not altered significantly during acetylcholine infusion in either of the two groups. Both whole kidney and superficial filtration fractions decreased significantly. At spontaneous arterial pressures, transglomerular hydrostatic pressure was not altered significantly because of equivalent increases in proximal tubule pressure and in glomerular pressure. In the dogs studied at reduced renal perfusion pressure, glomerular capillary pressure did not change, but proximal tubule pressure increased slightly. Average effective filtration pressures and Kf were not significantly altered during the infusion of acetylcholine either at spontaneous or reduced renal perfusion pressures. These observations indicate that Kf in the dog is not significantly decreased by acetylcholine and that GFR is not affected during infusion of this agent because the effective filtration pressure is not significantly altered.

Acetylcholine↗
PubMed1983

Effects on renal hemodynamics of intra-arterial infusions of angiotensins I and II.

Experiments were conducted in anesthetized dogs to evaluate the differences between the effects of intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) and those of circulating ANG II on renal blood flow (RBF), glomerular filtration rate (GFR), peritubular capillary pressure (PCP), proximal tubular free-flow pressure (PTP), and stop-flow pressure (SFP). Equiconstrictor doses of ANG I and ANG II were infused into the renal arteries of dogs kept on normal and high sodium diets. In clearance experiments, RBF decreased by 23% (low dose) and 33% (high dose) during the infusion of either ANG I or ANG II; GFR was significantly reduced only during the ANG I infusion. In micropuncture experiments, in which the GFR responses were similar, there were significant reductions in PTP (23 +/- 3%) and PCP (33 +/- 3%) during the intrarenal ANG I infusion; SFP was not altered significantly. Afferent and efferent arteriolar resistances increased significantly during ANG I infusion as well as during infusion of ANG II. These results indicate that during intra-arterial infusion of ANG I, the conversion to ANG II within the kidney occurs early enough to decrease glomerular filtration rate through an apparent increase in preglomerular resistance.

Angiotensin I↗
PubMed1983

Intrarenal angiotensin I conversion at normal and reduced renal blood flow in the dog.

Intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) under conditions of normal and reduced renal blood flow (RBF) elicited by constriction of the renal artery was examined in pentobarbital-anesthetized dogs. In eight animals, tracer doses of 125I-ANG I (5-12 pmol) were injected into the renal artery and 125I-ANG I, 125I-ANG II, and 125I-labeled metabolites were measured in renal venous effluent by high-voltage paper electrophoresis. The mean conversion of ANG I to ANG II during a single passage through the kidney was 21.8 +/- 2.1% at control RBF. When RBF was decreased by 25 and 53%, percent ANG I conversion was not altered significantly. In six dogs percent conversion of 125I-[Sar1, Ile5]ANG I, an ANG I analogue refractory to hydrolysis by aminopeptidases, was 18.1 +/- 1.7% at control RBF and did not change significantly when the RBF was reduced by 55%. Although there were severalfold increases in renal renin secretion rate and net ANG I generation rate during reduced RBF, net renal ANG II formation rate did not change significantly. These data indicate that there is substantial conversion of ANG I in a single passage through the dog kidney and that intrarenal ANG I conversion is independent of RBF even under conditions in which renin secretion rate and ANG I generation rate are increased severalfold.

Angiotensin I↗
PubMed1983

Renal hemodynamic effects of captopril in anesthetized sodium-restricted dogs. Relative contributions of prostaglandin stimulation and suppressed angiotensin activity.

The mechanism of captopril-induced alterations in arterial pressure (AP), glomerular filtration rate (GFR), renal blood flow (RBF), and renal vascular resistance (RVR) was studied in pentobarbital anesthetized sodium-restricted dogs. In 7 dogs, captopril caused decreases in AP (16 +/- 3%) and RVR (46 +/- 5%), as well as increases in RBF (62 +/- 12%) and sodium excretion (399 +/- 73%). These responses were reversed by angiotensin II infusion at a rate sufficient to restore RBF to control levels. The captopril-induced increase in GFR (29 +/- 8%) was partially reversed by the intravenous angiotensin II infusion to a level not significantly different from control. In 5 dogs, indomethacin increased AP (10 +/- 2%) and RVR (38 +/- 8%); the slight decreases in RBF and GFR were not statistically significant. Subsequent captopril treatment decreased AP (20 +/- 3%) and RVR (42 +/- 4%), while RBF and GFR increased by 45 +/- 8% and 32 +/- 10%, respectively. These observations suggest that the renal response to captopril in sodium-restricted dogs is not dependent upon alterations in prostaglandin synthesis but, instead, is primarily due to diminished angiotensin II activity.

Angiotensin II↗
PubMed1982

Cytoplasmic calcium in the mediation of macula densa tubulo-glomerular feedback responses.

Within each nephron of the mammalian kidney, a feedback mechanism operating between the macula densa segment of the distal tubule and the afferent arteriole participates in the regulation of glomerular filtration rate. Retrograde microperfusion studies in rats were conducted to test the hypothesis that activation of macula densa cytoplasmic calcium is involved in the transmission of feedback signals to the vascular elements. Perfusion into distal tubules with a hypotonic solution (70 milliosmolar) elicited moderate decreases in glomerular pressure of 6 +/- 0.8 millimeters of mercury. With the addition of a calcium ionophore (A23187) glomerular pressure decreased by 16 +/- 1.1 millimeters of mercury. When a solution devoid of calcium but containing A23187 was used, the feedback response was inhibited. Thus, cytoplasmic calcium within the receptor cells may participate in the transmission of feedback signals to the contractile cells.

Animals↗
PubMed1982

Relationship between tubulo-glomerular feedback responses and perfusate hypotonicity.

Previous studies have established that during orthograde perfusion from a late proximal tubule site, there is a direct relationship between the magnitude of the feedback response and the level of distal tubular fluid sodium chloride concentration. The present study was conducted in the rat to extend this observation by assessing stop flow pressure (SFP) feedback responses during retrograde perfusion into the early distal tubule with solutions varying in total solute concentration and in the anionic constituent. SFP was measured after blockade of the intermediate proximal and late distal tubular segments with wax. Retrograde perfusion was initiated from an early distal tubular site at 15 nl/min. All solutions contained a 38 mOsm/kg matrix base, and the total solute concentration was increased with either sodium chloride or sodium isethionate to achieve osmolalities of 68, 85, and 120 mOsm/kg. For comparison, feedback responses during perfusion with a 120 mOsm/kg choline chloride solution were evaluated. During perfusion with the 120 mOsm/kg solutions, SFP decreased by 13 +/- 1.3 mm Hg with the sodium chloride solution, 12 +/- 1.5 mm Hg with the sodium isethionate solution, and 12 +/- 1.3 mm Hg with the choline chloride solution. During perfusion with solutions having an osmolality of 85 mOsm/kg, SFP decreased by 8 +/- 1.3 mm Hg with sodium chloride and 8 +/- 0.8 mm Hg with sodium isethionate. The 68 mOsm/kg solutions elicited decreases in SFP of 4.4 +/- 0.4 mm Hg and 5 +/- 0.5 mm Hg. During perfusion with the 38 mOsm/kg matrix solution, SFP decreased by an average of 1.4 +/- 0.9 mm Hg. Linear regression analysis revealed a 1 mm Hg decrease in SFP for every 7.7 mOsm/kg decrease in perfusate osmolality below 120 mOsm/kg. These results confirm previous findings that the magnitude of the feedback response is associated closely with the concentration of the perfusate over a narrow range from 38 to 120 mOsm/kg. Since the responses with sodium isethionate solutions were similar to the responses obtained with sodium chloride containing solutions, these studies provide evidence that the magnitude of the feedback responses are not specifically dependent on alterations in chloride concentration.

Animals↗
PubMed1982

Attenuated pressure natriuresis in hypertensive rats.

We studied the isolated blood-free perfused nonclipped kidneys from the 2-kidney Goldblatt hypertensive rat model (GHR) to evaluate intrinsic excretory responses to changes in perfusion pressure. We examined kidneys from 10 control rats (in vivo systolic BP 110 +/- 3.6 mm Hg), from 9 rats with nonmalignant hypertension (HBP) (in vivo systolic BP 158 +/- 6.5 mm Hg), and from 5 rats with malignant HBP (in vivo systolic BP 183 +/- 6.4 mm Hg). We found that at all levels of perfusion pressure, the renal vascular resistances were significantly higher and glomerular filtration rate (GFR) lower in kidneys from hypertensive rats than in kidneys from control rats. Kidneys from hypertensive rats had lower urinary excretion of sodium (UNaV) and urine flow than kidneys from control rats at all levels of pressure above 100 mm Hg. The most striking differences in all functional parameters were noted in kidneys from rats with malignant HBP. Kidneys from both hypertensive and control rats failed to show changes in vascular resistance in response to Saralasin. We conclude that the nonclipped kidney in GHR exhibits a blunted natriuresis in response to elevated perfusion pressure which occurs in the absence of angiotensin II (AII) and renin substrate. This diminished pressure natriuresis may be caused partly by the lower GFR and by reduced pressure transmission due to greater renal vascular resistance and thus may be partially responsible for the maintenance of the hypertensive state.

Animals↗
PubMed1982

Effects of saralasin infusion on bilateral renal function in two-kidney, one-clip Goldblatt hypertensive rats.

1. Previous studies have shown that administration of converting enzyme inhibitor (CEI, SQ 20 881) to two-kidney, one-clip Goldblatt hypertensive (GH) rats clipped for 3-4 weeks resulted in marked increases in glomerular filtration rate (GFR), water and sodium excretion by the non-clipped kidneys. The clipped kidneys exhibited reduced function that was due, in part, to the reductions in arterial pressure. To evaluate further the hypothesis that the renal responses to CEI were due primarily to the inhibition of angiotensin II rather than other factors, we infused the angiotensin II competitive blocker, saralasin, into GH rats under sodium pentobarbital anaesthesia and examined renal haemodynamics and excretory function of each kidney before and during saralasin infusion and after cessation of saralasin infusion. 2. Saralasin reduced mean arterial blood pressure from 164 +/- 4 to 124 +/- 4 mmHg. Despite the profound fall of arterial pressure, significant increases in renal blood flow from 5.82 +/- 0.22 to 9.15 +/- 0.76 ml/min and glomerular filtration rate from 1.46 +/- 0.10 to 2.18 +/- 0.14 ml/min were observed in the non-clipped kidneys. Renal vascular resistance decreased from 2.34 (+/- 0.14) x 10(5) to 1.17 (+/- 0.19) x 10(5) kPa 1(-1) s [2.34 (+/- 0.14) x 10(6) to 1.17 (+/- 0.19) x 10(6) dyn s cm-5]. Also, concomitant diuresis and kaliuresis and a delayed natriuresis occurred. 3. The clipped kidneys exhibited reductions in renal blood flow, GFR and excretory function during saralasin infusion. 4. Normal rats receiving the identical dose of saralasin responded with a slight but significant decrease in arterial pressure. The increase in renal blood flow and GFR were less than those observed in the non-clipped kidneys of hypertensive rats. 5. These data provide further support to the hypothesis that an angiotensin II-mediated elevation in renal vascular resistance and impairment of renal function exist in the non-clipped kidneys of GH rats.

Angiotensin II↗
PubMed1982

Angiotensin-mediated alterations in nephron function in Goldblatt hypertensive rats.

The present study was performed to evaluate superficial nephron responses of the nonclipped kidney to angiotensin I converting enzyme inhibitor (CEI) (SQ 20,881, 3 mg . kg-1 . h-1) in two-kidney, one-clip Goldblatt hypertensive (GH) rats. Late proximal and early distal tubule collections were obtained before and during CEI. Significant increases in glomerular filtration rate, urine flow, sodium excretion, proximal and distal tubule flow rates, and single nephron glomerular filtration rate (from 24.6 +/- 1.7 to 27.5 +/- 1.6 nl/min) occurred despite reductions in arterial blood pressure (from 160 +/- 5 to 137 +/- 6 mmHg) during CEI. Proximal tubule absolute and fractional reabsorption of fluid, chloride, and total solute decreased significantly. In the nephron segment between the two collection sites, there were increases in absolute but decreases in fractional reabsorption. At the distal tubule level, fractional reabsorption but not absolute reabsorption decreased significantly. Proximal and distal tubule hydrostatic pressures increased significantly while peritubular capillary pressure decreased slightly. Responses following inhibition of angiotensin II formation suggest that there exists an angiotensin II-mediated enhancement in tubular reabsorption in the nonclipped kidney of Goldblatt hypertensive rats.

Administration, Topical↗
PubMed1982

Influence of bradykinin and papaverine on renal and glomerular hemodynamics in dogs.

Although it is recognized that vasodilator-induced increases in renal plasma flow are not associated with increases in glomerular filtration rate (GFR), the mechanism responsible for the failure of GFR to exhibit plasma flow dependency under these circumstances remains uncertain. To evaluate this problem further, the effects of intra-arterial infusion of two vasodilators, bradykinin (n = 7) and papaverine (n = 6), on renal hemodynamics and glomerular function of dogs were determined. Both agents increased renal blood flow; however, GFR and single nephron GFR (SNGFR) remained unchanged during bradykinin infusion and decreased significantly during papaverine infusion. Transglomerular hydrostatic pressure and mean effective filtration pressure were not altered during bradykinin infusion but were significantly reduced by papaverine. Neither agent altered the glomerular filtration coefficient. These observations indicate that, in the dog, the GFR responses during renal vasodilation are dependent primarily on the effective filtration pressure.

Animals↗