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Biomedical subjects

L G Navar

Publications and source records attributed to L G Navar.

At least 127 records · Page 7Linked to original sources
PubMed1990

Single-nephron adaptations to partial renal ablation in the dog.

Micropuncture and histological studies were performed in dogs to characterize single-nephron adaptations to partial renal ablation. Dogs underwent sham surgery (group 1, n = 6), three-fourths nephrectomy (group 2, n = 10), or seven-eighths nephrectomy (group 3, n = 6). Single-nephron glomerular filtration rate (SNGFR) was 71.0 +/- 4.2 nl/min in group 1, 132.5 +/- 9.6 nl/min in group 2, and 161.8 +/- 12.4 nl/min in group 3 (P less than 0.05). There were parallel increases in single-nephron glomerular plasma flow rate (GPF), with a mean value of 235.3 +/- 20.1 nl/min in group 1, 442.4 +/- 34.4 nl/min in group 2, and 569.6 +/- 73.7 nl/min in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). Glomerular capillary pressure, estimated from the sum of proximal tubule stop-flow pressure and arterial oncotic pressure, was 63.2 +/- 1.9 mmHg in group 1, 73.5 +/- 2.0 mmHg in group 2, and 77.9 +/- 2.2 mmHg in group 3 (P less than 0.05, group 1 vs. groups 2 and 3). The mean glomerular transcapillary hydraulic pressure gradient (delta P) in group 2 was not different from group 1 (46.8 +/- 1.3 vs. 43.9 +/- 1.8 mmHg, NS); however, it was significantly increased in group 3 (50.0 +/- 1.4 mmHg; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1990

Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers.

Experiments were performed in pentobarbital-anesthetized rats to evaluate the dependence of the effector limb of the tubuloglomerular feedback mechanism on transmembrane calcium flux through potential-operated calcium channels. Peritubular capillary infusions of the calcium channel blockers, verapamil and nifedipine, were used to achieve high intrarenal levels without influencing arterial blood pressure. Proximal tubule stop-flow pressure (SFP) and single-nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses were obtained during control conditions and during simultaneous peritubular capillary infusion with an isotonic saline solution containing either verapamil or nifedipine. Infusion of either 10(-3) M verapamil or 10(-3) M nifedipine, at a rate of 20 nl/min, increased resting SFP (measured during conditions of zero distal volume delivery) and markedly attenuated both the SFP and SNGFR feedback responses to a late proximal perfusion rate of 30 nl/min. Infusion of verapamil (10(-3) M) also increased the slope of the relationship between SFP and renal arterial perfusion pressure between 80 and 120 mmHg (0.43 +/- 0.03 vs 0.24 +/- 0.02, P less than 0.001, n = 10). These findings support the hypothesis that the preglomerular contractile elements responsive to signals from the macula densa cells are activated by calcium influx through potential-operated calcium channels. Furthermore, the preglomerular contractile elements sensitive to calcium channel blockers can dilate further even when orthograde flow to a single macula densa segment is interrupted.

Animals↗
PubMed1990

Angiotensin II stimulation of Na(+)-H+ exchange in proximal tubule cells.

Experiments were performed to evaluate the effect of angiotensin II (ANG II) on the sodium transport activity of isolated intact rabbit proximal tubule cells. Initial rates of 22Na(+) uptake were measured in Na+-depleted and ouabain-treated cells in the presence of an opposing H+ gradient (pHin less than pHout). ANG II (10(-12)-10(-9) M) stimulated the initial rate of 22Na+ uptake by 33 +/- 2%, whereas amiloride (0.5 mM) inhibited both basal and ANG II-stimulated 22Na+ uptake. ANG II-stimulated rate of 22Na+ uptake was inhibited by the receptor antagonist saralasin. Additional experiments were performed to evaluate the effect of ANG II on the rate of recovery of pHin in acid-loaded proximal tubule cells. Cells were acid loaded by an NH4Cl pulse in the presence of the pH-sensitive fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. ANG II increased the initial rate of intracellular alkalinization, and this effect was inhibited by amiloride (1.0 mM). ANG II stimulation increased the Vmax of H+ efflux (from 0.53 +/- 0.02 to 0.64 +/- 0.04 pH units/min) without changing the Km for extracellular Na+. The present findings indicate that physiological concentrations of ANG II stimulate an amiloride-sensitive Na+-H+ antiport in proximal tubule cells.

Alkalies↗
PubMed1990

Prostaglandin influences on afferent arteriolar responses to vasoconstrictor agonists.

The present study was designed to evaluate, at the microvascular level, the ability of prostaglandins E2 (PGE2) and I2 (PGI2) to counteract the afferent vasoconstrictor effects of angiotensin II (ANG II) and norepinephrine (NE). The renal microvasculature of rats pretreated with captopril and indomethacin was studied directly by use of the in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy. Afferent arterioles averaged 22.7 +/- 0.6 microns ID (n = 59) under control conditions. Topical administration of PGE2 revealed a concentration-dependent afferent vasoconstriction, whereas PGI2 (10(-7) to 10(-5) M) failed to significantly alter afferent arteriolar diameter. Afferent arterioles constricted during exposure to either 10(-9) M ANG II (-15 +/- 3%, n = 13) or 10(-7) M NE (-19 +/- 3%, n = 13). Addition of PGE2 (10(-6) M) to the bathing solution enhanced the vasoconstrictor influences of ANG II and NE by an additional 18 +/- 6 and 13 +/- 4%, respectively. In contrast, while 10(-6) M PGI2 had no effect on ANG II-induced afferent vasoconstriction, it did produce a 30% attenuation of NE-induced constriction. Furthermore, pretreatment of the tissue with 10(-6) M PGI2 prevented development of NE-induced afferent vasoconstriction. Thus, although local tissue prostanoid concentrations are unknown, it appears that low micromolar concentrations of PGE2 elicit an afferent arteriolar constriction that can accentuate the vascular actions of ANG II and NE on rat juxtamedullary afferent arterioles. In contrast, PGI2 can counteract the vasoconstrictor response to NE, but not ANG II, in this experimental setting.

Afferent Pathways↗
PubMed1990

Single-nephron responses to systemic administration of amino acids in dogs.

It has been suggested that the tubuloglomerular feedback (TGF) system is responsible for renal vasodilation during systemic infusion of amino acid solutions. We evaluated the effect of intravenous administration of amino acids (serine, alanine, proline, and glycine; total dose of 0.075 mmol of amino acids.kg body wt-1.min-1) on whole kidney and single-nephron hemodynamics in pentobarbital sodium-anesthetized dogs. At spontaneous renal arterial pressure (RAP; 125.4 +/- 4.7 mmHg), measurements of single-nephron function obtained during tubular blockade, stop-flow pressure (SFP; 48.2 +/- 2.0 vs. 58.9 +/- 2.3 mmHg, P less than 0.01), and proximally determined single-nephron glomerular filtration rate (SNGFR-TPC; 73.9 +/- 7.0 vs. 93.4 +/- 7.6 nl/min, P less than 0.01) increased in parallel to the increases of outer cortical blood flow (OCBF; 15.4 +/- 1.1 vs. 19.1 +/- 1.5 units, P less than 0.05), renal blood flow (RBF; 4.60 +/- 0.18 vs. 5.73 +/- 0.22 ml.min-1.g kidney wt-1, P less than 0.01), and glomerular filtration rate (GFR; 0.885 +/- 0.034 vs. 1.116 +/- 0.034 ml.min-1.g kidney wt-1, P less than 0.01). Free-flow tubular fluid-to-plasma inulin ratios, determined from late proximal recollections during saline (control) and amino acid infusions failed to provide evidence for altered proximal reabsorption rate (1.63 +/- 0.12 vs. 1.58 +/- 0.17 during amino acids, NS). At reduced RAP (92.6 +/- 1.9 mmHg), where it is presumed that TGF-mediated vasodilation is already near maximal, the vasodilatory response to amino acid infusion was intact and single-nephron parameters measured during tubular blockade increased to the same extent as OCBF, RBF, and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1990

Afferent arteriolar responsiveness to altered perfusion pressure in renal hypertension.

The present study was performed to determine the role of afferent arterioles in the impaired autoregulatory response shown to occur in the contralateral kidney of Goldblatt hypertensive rats. The responsiveness of juxtamedullary afferent arterioles to alterations in perfusion pressure was studied in the nonclipped kidney of two-kidney, one clip hypertensive and sham-operated rats. Systolic pressure, 5-6 weeks after clipping, averaged 184 +/- 6 mm Hg in the hypertensive rats (n = 16) and 121 +/- 3 mm Hg in the sham-operated control rats (n = 7). By using the in vitro blood-perfused juxtamedullary nephron technique, afferent arterioles were directly visualized, and their inside diameters were measured by videomicroscopic methods. In sham-operated kidneys perfused with blood from normotensive rats, afferent arteriolar diameter averaged 22.8 +/- 1.8 microns at a renal arterial perfusion pressure of 151 +/- 1 mm Hg and increased to 24.8 +/- 1.8 microns when perfusion pressure was reduced to 110 +/- 2 mm Hg. Conversely, in hypertensive kidneys perfused with blood from either hypertensive or normotensive rats, the afferent arterioles failed to vasodilate and actually exhibited a slight decrease in diameter from 24.6 +/- 1.3 to 23.0 +/- 2.3 microns in response to the same reduction in perfusion pressure. Vasodilator capability, however, could be demonstrated in response to verapamil and sodium nitroprusside, which increased afferent diameter in both the sham-operated and hypertensive groups of rats. Thus, unlike arterioles from normotensive rats, juxtamedullary afferent arterioles from two-kidney, one clip Goldblatt hypertensive rats fail to vasodilate after a reduction in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to ANG II.

Previous reports have suggested that organic calcium antagonists only partially inhibit the renal hemodynamic actions of angiotensin II (ANG II). This study tested the hypothesis that the calcium antagonist-sensitive component of ANG II-induced vasoconstriction is localized at a preglomerular site. Videomicroscopic measurements of vascular dimension were performed on in vitro blood-perfused juxtamedullary nephrons from captopril-treated rats. Under control conditions, afferent and efferent arteriolar diameters averaged 23.0 +/- 1.6 and 21.2 +/- 2.2 microns, respectively. Topical application of 0.1 nM ANG II decreased the diameters of afferent (-17 +/- 2%) and efferent (-15 +/- 3%) arterioles. Both 50 microM verapamil and 10 microM diltiazem dilated afferent arterioles. Verapamil also elicited a modest efferent vasodilation. In the presence of either verapamil or diltiazem, the effect of ANG II to decrease efferent diameter was sustained (-15 +/- 4%); however, the effect of ANG II on afferent diameter was abolished (-1 +/- 1%). These observations document differential influences of calcium channel blockers on ANG II-mediated vasoconstriction and suggest that the pre- and postglomerular vasoconstrictor actions of ANG II may occur through different calcium entry or mobilization mechanisms.

Angiotensin II↗
PubMed1989

Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism.

To evaluate further the role of adenosine in the transmission of tubuloglomerular feedback signals, we studied the effects of an adenosine receptor antagonist and an adenosine A1-receptor agonist on feedback-mediated changes in stop-flow pressure (SFP). In orthograde perfusion experiments conducted in anesthetized rats, systemic administration of the adenosine receptor blocker 1,3-dipropyl-8-sulfophenylxanthine (PSPX) did not inhibit feedback responses. Control SFP feedback responses averaged 9.7 +/- 0.65 before and 8.6 +/- 0.55 mmHg during systemic infusion of the receptor blocker. In retrograde perfusion experiments, intratubular administration of the A1 agonist (360 nM) N6-cyclopentyladenosine (CPA), added to a hypotonic solution, markedly enhanced feedback responses. This effect was completely prevented by coinfusion of PSPX. Addition of 10 mM of the antagonist to the CPA-containing solution attenuated SFP feedback responses to less than 1 mmHg (delta = 0.44 +/- 0.50). Furthermore, PSPX also inhibited feedback responses obtained with an isotonic solution alone. Furosemide, which has been shown to block normal SFP responses obtained with isotonic solutions, failed to block CPA-induced decreases in SFP. These data demonstrate that intraluminal administration of an adenosine A1 analogue causes feedback-mediated decreases in SFP and therefore support a role for adenosine receptors in the signal transmission pathway.

Adenosine↗
PubMed1988

Angiotensin influences on tubuloglomerular feedback mechanism in hypertensive rats.

The tubuloglomerular feedback (TGF) mechanism was evaluated in the nonclipped kidney of Goldblatt hypertensive rats from both stop flow pressure (SFP) and single nephron glomerular filtration rate (SNGFR) responses to step increases in late proximal perfusion rate from 0 to 40 nl/min. During control conditions, increases in late proximal perfusion rate produced flow dependent decreases in SFP and SNGFR with maximal values of 10.2 +/- 1.0 mm Hg and 12.9 +/- 2.5 nl/min, values similar to those obtained in normal rats. During ACE inhibition (MK 422; 0.6 mg/kg/hr), arterial pressure decreased from 168 +/- 8 to 137 +/- 7 mm Hg and there was a marked attenuation in the magnitude of SFP feedback responses (delta = 2.5 +/- 0.3 mm Hg). SNGFR feedback responses, however, were not significantly impaired. Direct decreases in renal arterial pressure reduced control SFP but SFP feedback responses were maintained, indicating that the attenuated SFP feedback responses during ACE inhibition were not due to decreased arterial pressure. Superimposed infusion of angiotensin II during ACE inhibition partially restored SFP feedback responses. In contrast, norepinephrine infusion did not result in a similar restoration of SFP feedback sensitivity. These results indicate that the nonclipped kidney of Goldblatt hypertensive rats has an intact TGF mechanism as assessed from SFP and SNGFR feedback responses. Furthermore, ACE inhibition attenuates SFP but not SNGFR feedback responses, and systemic angiotensin II infusions can restore SFP feedback responsiveness towards normal.

Angiotensin II↗
PubMed1988

Direct evaluation of the microvascular actions of ANP in juxtamedullary nephrons.

The renal vascular actions of atrial natriuretic peptide (ANP) remain incompletely understood. The purpose of this study is to evaluate the effects of ANP on microvascular structures of the normal kidney. The in vitro blood-perfused juxtamedullary nephron technique was utilized to allow visualization of arcuate arteries and afferent and efferent arterioles. Donor rats were pretreated with captopril to eliminate possible interactions between angiotensin II and atriopeptin III (AP III). The effects of topical administration of 3 nM AP III were determined by videometric analysis of vessel inside diameters. Under control conditions, arcuate arterial diameter averaged 83 +/- 14 microns (n = 7), afferent arteriolar diameter was 20 +/- 4 microns (n = 7), and efferent arteriolar diameter was 16 +/- 2 microns (n = 7). During superfusion with AP III, arcuate arteries and afferent arterioles dilated 73 +/- 9 and 23 +/- 5%, respectively. Both returned to their control values when AP III was removed from the superfusate. Further experiments on arcuate arteries (n = 5) revealed that 0.3 nM AP III also vasodilated these vessels (26 +/- 9%); however, no significant effect was elicited by 0.03 nM AP III. In contrast to the vasodilator influence of AP III on preglomerular vessels, efferent arteriolar diameter was not altered by AP III exposure. These observations reveal that AP III can induce selective preglomerular vasodilation involving arcuate arteries as well as afferent arterioles, while efferent arteriolar diameter is not perceptibly influenced.

Animals↗
PubMed1988

Evaluation of prostaglandins as mediators of tubuloglomerular feedback.

Orthograde and retrograde microperfusion experiments were conducted in Sprague-Dawley rats to evaluate the participation of vasoconstrictive eicosanoids as mediators of tubuloglomerular feedback (TGF) signals. Retrograde perfusion with 160 microM arachidonic acid (AA) added to a hypotonic solution enhanced the stop-flow pressure (SFP) feedback responses compared with those obtained with the control hypotonic solution (delta SFP, 1.6 +/- 0.4 vs. 10.1 +/- 0.7 mmHg with AA). Blockade of thromboxane A2 (TxA2) with the receptor blocker EP 092 or the synthesis inhibitor UK 38485 did not alter the magnitude of the SFP feedback responses obtained with an isotonic solution. Similarly, nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not alter maximal SFP feedback responses. Although indomethacin (5 mM) did induce attenuated SFP feedback responses (delta SFP, 9.5 +/- 0.7 vs. 0.5 +/- 0.4 mmHg with indomethacin), normal feedback responses were restored within 15-90 s after cessation of indomethacin perfusion. Additionally, SFP feedback responses were not inhibited with 5 mM piroxicam, a different cyclooxygenase inhibitor. These data fail to support a role for either TxA2 or lipoxygenase end products as mediators of TGF signals. The rapid restoration of feedback responses after indomethacin exposure and the lack of blockade with piroxicam suggest that transmission of feedback signals is not dependent on cyclooxygenase products.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Enhanced tubuloglomerular feedback during peritubular infusions of angiotensins I and II.

Experiments were performed in pentobarbital sodium-anesthetized rats to determine whether increases in intrarenal generation of angiotensin II (ANG II) can enhance the sensitivity of the tubuloglomerular feedback mechanism. Stop-flow pressure (SFP) feedback responses to step increases in late proximal perfusion rate were obtained during control conditions and during simultaneous peritubular capillary infusion of either angiotensin I (ANG I) or ANG II. Infusion of either 10(-7) M ANG II or 10(-5) M ANG I, at rates (18.3 +/- 0.9 and 14.8 +/- 1.5 nl/min, respectively) that did not affect resting SFP, enhanced the magnitude of SFP feedback responses both at a low proximal perfusion rate of 10 nl/min (2.9 +/- 0.9 vs. 0.3 +/- 0.2 and 4.5 +/- 1.0 vs. 0.1 +/- 0.1 mmHg, respectively) and at proximal perfusion rates (greater than 30 nl/min) that elicited a maximal feedback response (13.1 +/- 1.0 vs. 10.1 +/- 0.7 and 13.5 +/- 1.6 vs. 9.8 +/- 0.8 mmHg, respectively). With a higher ANG I infusion rate (20 nl/min), control SFP measured in the absence of distal volume delivery decreased from 39.2 +/- 0.6 to 12.0 +/- 2.8 mmHg (n = 18). These effects were blocked when the ANG II receptor antagonist, saralasin (10(-5) M, Sar), was added to the infusate. In addition, the magnitude of the maximal SFP feedback response was not altered during infusion of Sar alone or ANG I + Sar. These findings indicate that ANG II, either added or formed de novo beyond the glomerular circulation, can enhance the sensitivity of the tubuloglomerular feedback mechanism.

Angiotensin I↗
PubMed1988

ANF secretion and renal responses to volume expansion with equilibrated blood.

To evaluate the role of atrial natriuretic factor (ANF) in the renal response to acute blood volume expansion without hemodilution, a reservoir syringe filled with donor rat blood was connected to the femoral artery and vein of anesthetized Sprague-Dawley rats to allow rapid equilibration of the reservoir with the intravascular blood. Volume expansion with blood from the reservoir in two steps (of 1 and 1.5% body wt, separated by 1 h, n = 5 rats) produced a mean peak increase in plasma immunoreactive ANF from 99 +/- 21 to 1,310 +/- 230 pg/ml (P less than 0.001); plasma ANF levels throughout these experiments correlated significantly with simultaneously measured urine flow (r = 0.74, P less than 0.005) and sodium excretion (r = 0.65, P less than 0.005). Another group (n = 7) underwent the same two-step procedure; after the second volume expansion, high-dose atriopeptin III infusion (0.4 microgram.kg-1.min-1 did not further increase fractional excretion of sodium (3.17 +/- 0.27 to 2.50 + 0.39%, P = NS). In another group (n = 9 rats), the same dose of atriopeptin III was started before any blood volume expansion. After the resulting hypotension was corrected by restoration of blood volume, an additional 1.5% body weight blood volume expansion did not further augment sodium excretion. We conclude that the diuresis and natriuresis, which occur in response to volume expansion without hemodilution, rise and fall in parallel with immunoreactive ANF in the plasma, and that ANF and acute blood volume expansion act on the kidney through a similar, saturable mechanism.

Animals↗
PubMed1988

Tubuloglomerular feedback-dependent influence of angiotensin II on the kidney in rats.

To examine the modulatory role of angiotensin II on the tubuloglomerular feedback (TGF) mechanism, TGF responses were assessed during control conditions, converting enzyme inhibition (CEI; MK 422, 0.6 mg/kg.hr) and during continued CEI with the replacement of angiotensin II. TGF responses were assessed from stop flow pressure (SFP) feedback responses obtained during step increases in the late proximal perfusion rate from 0-40 nl/min. SFP values in the absence of perfusion were used to estimate glomerular pressure (GP) under conditions where the influence of the TGF mechanism should be at a minimum. During CEI, the arterial pressure decreased from 124 +/- 3 to 106 +/- 3 mmHg and the estimated GP decreased from 53 +/- 1.4 to 49 +/- 0.8 mmHg. There was a marked attenuation in the magnitude of SFP feedback responses from 11.0 +/- 1.3 to 2.7 +/- 0.6 mmHg. TGF feedback responses, however, were restored towards normal during superimposed angiotensin II infusion (7.7 +/- 0.9 mmHg). These results indicate that converting enzyme inhibition decreases the effects of angiotensin II on the kidney through TGF dependent mechanism.

Angiotensin II↗