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K D Mitchell

Publications and source records attributed to K D Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Role of bradykinin B2 receptors in the developmental changes of renal hemodynamics in the neonatal rat.

The present study was performed to evaluate the role of bradykinin, acting via B2 receptors, in the developmental rise in renal blood flow (RBF) and glomerular filtration rate (GFR) in the rat. Newborn rats were chronically treated from birth with the kinin B2 receptor antagonist HOE-140 (600 micrograms/kg sc, every 12 h, n = 9) or 0.9% saline (n = 7). Weanling rats (mean age 23 days) were anesthetized with pentobarbital sodium (50 mg/kg ip) for measurements of mean arterial pressure (MAP), GFR, and renal plasma flow estimated from p-aminohippurate (PAH) clearance (ERPF). Outer cortical RBF (OCBF) was measured by laser-Doppler flowmetry. Baseline MAP was similar in HOE-140- and saline-treated rats (96 +/- 4 vs. 97 +/- 4 mmHg). Also, baseline GFR (0.65 +/- 0.05 vs. 0.52 +/- 0.08 ml.min-1.g-1) and ERPF (1.6 +/- 0.2 vs. 1.3 +/- 0.1 ml.min-1.g-1) were not different in HOE-140- and saline-treated rats, respectively. Intravenous infusion of 200 ng bradykinin did not change MAP or OCBF in HOE-140 rats but decreased MAP (-29 +/- 3%, P < 0.05) and OCBF (-20 +/- 2%, P < 0.05) in controls. Intravenous infusion of 25 ng angiotensin II increased MAP equally in both groups (-32 +/- 4%) and caused a similar reduction in OCBF (-37 +/- 14 vs. -46 +/- 5%). The angiotensin type 1 (AT1) receptor antagonist losartan (10 mg/kg iv) decreased MAP equally in both groups (-22 +/- 2%). However, AT1 blockade increased ERPF to 3.1 +/- 0.8 ml.min-1.g-1 (P < 0.05 vs. baseline) in saline but not in HOE-140 rats (1.9 +/- 0.4 ml.min-1.g-1). Kidney renin mRNA and angiotensin II contents were not different in HOE-140 vs. saline groups. The present findings indicate that bradykinin is not a primary mediator of the maturational rise in RBF or GFR in the rat. However, the data suggest that under control conditions, angiotensin II, acting via AT1 receptors, counteracts the renal vasodilatory effects of endogenous bradykinin in the developing kidney.

Angiotensin II↗
PubMed1995

Modulation of tubuloglomerular feedback by angiotensin II type 1 receptors during the development of Goldblatt hypertension.

It has been suggested that the increased levels of angiotensin II (Ang II) in the contralateral kidney of two-kidney, one clip (2K1C) Goldblatt hypertensive rats act to enhance tubuloglomerular feedback responsiveness and proximal tubular reabsorption and thereby exert a substantial sodium-retaining influence on the nonclipped kidney. The current study investigated the Ang II dependency of tubuloglomerular feedback responsiveness in the nonclipped kidney during the early stages of development of 2K1C hypertension. Stop-flow pressure feedback responses were assessed in the nonclipped kidney of 2K1C rats during control conditions and after systemic administration of the Ang II type 1 receptor antagonist losartan (10 mg/kg). In 1-week clipped and sham-operated rats, losartan administration decreased mean arterial pressure (from 143 +/- 6 to 123 +/- 2 mm Hg, P < .01, and from 129 +/- 2 to 106 +/- 5 mm Hg, P < .01, respectively) and attenuated the magnitude of the maximal feedback responses (from -12.9 +/- 1.2 to -3.0 +/- 0.3 mm Hg, P < .01, and from -13.2 +/- 1.5 to -3.6 +/- 1.1 mm Hg, P < .01, respectively). The decreases in mean arterial pressure were not significantly different in sham-operated and 1-week clipped rats. In 3-week clipped rats, mean arterial pressure was further elevated (163 +/- 6 mm Hg) compared with sham-operated rats (134 +/- 4 mm Hg, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Enhancement of intrarenal angiotensin II levels in 2 kidney 1 clip and angiotensin II induced hypertension.

Previous studies have indicated that the hypertension that develops after unilateral arterial constriction (2 kidney, 1 clip) involves an active participation by the non-clipped contralateral kidney. Even though the non-clipped kidney is not the initial causative factors, and despite the progressive renin depletion during the early weeks following clipping, the non-clipped kidney is highly responsive to angiotensin blockers. Furthermore, the non-clipped kidney has augmented tissue ANG II levels and ACE activity suggesting that some renin-independent mechanism may be stimulating intrarenal ANG II formation. This model has been simulated by infusing ANG II at low subpressor doses (40 ng/min) to uninephrectomized rats for 14 days. With this model, plasma and renal renin levels are markedly suppressed; however, the renal ANG II levels are increased to levels above those that can be explained on the basis of circulating ANG II. In agreement with the responses observed in the non-clipped kidney of 2K1C rats, there is also an increased renal ACE activity. In contrast to the marked suppression of renin gene expression and renin activity, angiotensinogen gene expression is not suppressed. These results support the hypothesis that small elevations in circulating ANG II stimulate intrarenal ANG II production through a renin-independent mechanism.

Angiotensin II↗
PubMed1994

Extracellular ATP in the regulation of renal microvascular function.

Considerable attention has been focused on the purine nucleoside, adenosine, in the control of renal blood flow, epithelial transport, and renin secretion; however, surprisingly little attention has been directed toward the renal effects of purine nucleotides such as adenosine triphosphate (ATP). Recent studies utilizing in vivo micropuncture and in vitro techniques have demonstrated that renal vascular, epithelial, and mesangial cells respond to extracellular ATP via mechanisms distinct from those elicited by adenosine. ATP vasoconstricts afferent but not efferent arterioles whereas adenosine vasoconstricts both vascular segments. Adenosine-mediated afferent arteriolar vasoconstriction is abolished by adenosine receptor antagonists, whereas the response to ATP is enhanced. ATP-mediated vasoconstriction reaches a maximum within seconds of exposure while the vasoconstriction induced by adenosine develops more slowly. L-type calcium channel antagonists such as diltiazem or felodipine prevent the sustained afferent vasoconstriction produced by ATP. Data from micropuncture experiments indicate that peritubular capillary infusion of ATP reduces glomerular pressure and results in marked attenuation of the tubuloglomerular feedback mechanism, which transmits signals from the macula densa to the afferent arteriole. These data support the existence of ATP-sensitive P2 purinoceptors in the preglomerular microvasculature that contribute to the control of renal vascular function via activation of calcium channels.

Adenosine Triphosphate↗
PubMed1994

Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats.

Previous micropuncture studies have reported nanomolar concentrations of angiotensin II in proximal tubular fluid and have indicated that angiotensin II or a precursor may be secreted into the tubular lumen. Further experiments were performed to determine if proximal tubular fluid angiotensin I concentrations are also greater than plasma and kidney levels and to estimate the degree of intrarenal compartmentalization of the angiotensin peptides. Free-flow proximal tubular fluid samples were collected in micropipets and were pooled for each animal. At the end of each experiment, a blood sample was collected and the micropunctured left kidney was harvested and homogenized in methanol. The angiotensin I concentration in proximal tubular fluid samples averaged 6.1 +/- 1.2 pmol/mL, whereas the angiotensin II concentration averaged 8.1 +/- 1.6 pmol/mL (N = 13). HPLC analysis of a separate sample pooled from collections in five rats indicated that the immunoreactive angiotensin I and angiotensin II primarily represented authentic angiotensin I and II. Plasma concentrations of angiotensin I and angiotensin II averaged 0.39 +/- 0.09 and 0.15 +/- 0.03 pmol/mL, respectively. The kidney contents of angiotensin I and angiotensin II were 1.28 +/- 0.24 and 0.97 +/- 0.17 pmol/g of kidney, respectively. These findings indicate that proximal tubular fluid contains nanomolar concentrations of angiotensin I as well as angiotensin II. These high tubular fluid concentrations, which greatly exceed the plasma and kidney levels, likely reflect net secretion of the angiotensin peptides by proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1993

Modulation of tubuloglomerular feedback responsiveness by extracellular ATP.

Experiments were performed in pentobarbital sodium-anesthetized rats to determine the effects of activation of P2 purinoceptors sensitive to ATP on glomerular capillary pressure, as estimated from proximal tubule stop-flow pressure (SFP) measurements, and on the magnitude of maximal tubuloglomerular feedback-mediated reductions in SFP. To selectively expose nephrons in vivo to ATP without influencing arterial blood pressure, we infused ATP directly into the surrounding peritubular capillaries. Peritubular capillary infusion, at a rate of 20 nl/min, of an isotonic saline solution containing 10(-3) M ATP elicited a transient decrease in resting SFP. However, subsequent infusion of 10(-3) M ATP together with the adenosine receptor (P1 purinoceptor) antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (PSPX, 10(-3) M) into the same vascular sites elicited a sustained decrease in resting SFP. Peritubular infusion of the slowly metabolizable ATP analogue, beta,gamma-methylene-ATP (10(-3) M), at a rate of 20 nl/min, also elicited a transient decrease in SFP, but this was not converted to a sustained response by PSPX. The SFP feedback responses to a late proximal perfusion rate of 40 nl/min were markedly attenuated during peritubular infusion of either 10(-3) M ATP (8.7 +/- 1.2 vs. 1.8 +/- 0.9 mmHg; P < 0.01, n = 9) or 10(-3) M beta,gamma-methylene-ATP (8.2 +/- 1.3 vs. 2.2 +/- 1.2 mmHg; P < 0.01, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1993

Proximal tubular secretion of angiotensin II in rats.

It is now established that all of the components necessary for the local formation of angiotensin II (ANG II) coexist in the kidney and can alter local ANG II production rate. However, data on ANG II concentrations in different compartments within the kidney are limited. Recently, proximal tubule fluid ANG II concentrations in the nanomolar range were reported. Using an ANG II radioimmunoassay procedure with enhanced sensitivity, we performed experiments to explore proximal tubular fluid ANG II levels further and to determine the source of the ANG II. Total free-flow proximal tubular fluid samples (n = 11) had an average ANG II concentration of 13 +/- 2 nM. These concentrations were similar (10 +/- 2 nM) in samples collected into pipettes containing the inhibitors enalaprilat and EDTA (n = 17). Fluid collected from blocked proximal tubules that were perfused with artificial tubular fluid showed similar ANG II concentrations both in the presence (22 +/- 3 nM) and absence (22 +/- 4 nM) of the angiotensin-converting-enzyme inhibitor, enalaprilat, in the perfusate. Plasma ANG II concentrations were much lower and averaged 155 +/- 26 pM. Isotonic saline expansion lowered plasma ANG II levels to 30 +/- 5 pM (P < 0.01) but did not significantly decrease intraluminal ANG II (8 +/- 1 nM). These data provide further evidence that intratubular ANG II concentrations are in the nanomolar range and are regulated independently of the plasma ANG II levels. The data obtained from perfused tubules indicate that the proximal tubule adds substantial amounts of ANG II or a precursor into the tubular lumen.

Angiotensin II↗
PubMed1993

Contribution of angiotensin II to renal hemodynamic and excretory responses to nitric oxide synthesis inhibition in the rat.

This study was performed to evaluate the contribution of angiotensin II to the effects of nitric oxide (NO) synthesis inhibition on renal hemodynamics and excretory function in rats. Intravenous infusion of N omega-nitro-L-arginine (NLA; 20 micrograms/100 g.min) increased renal arterial pressure (RAP) from 128 +/- 2 to 143 +/- 3 mm Hg (P < 0.05; N = 6) and decreased RBF by 64 +/- 3% (P < 0.01) and GFR by 41 +/- 5% (P < 0.05). In response to reduction of RAP to control levels (127 +/- 2 mm Hg) by means of an adjustable clamp (CL) placed on the suprarenal aorta, RBF and GFR exhibited efficient autoregulation and were not altered. In rats (N = 6) pretreated with the AT1 angiotensin II receptor antagonist losartan (10 mg/kg iv), the infusion of NLA increased RAP (from 114 +/- 1 to 135 +/- 2 mm Hg; P < 0.05) and decreased RBF by 42 +/- 3% (P < 0.05). However, NLA did not decrease GFR in the losartan-treated rats. As in the control rats, the reduction of RAP to 113 +/- 1 mm Hg elicited autoregulatory responses that maintained RBF and GFR. In the untreated rats, at similar RAP (128 +/- 2 (control) versus 127 +/- 2 mm Hg (NLA+CL)). NO synthesis inhibition decreased urine flow and sodium excretion (P < 0.05, in both cases). However, during blockade of AT1 receptors, NLA infusion failed to decrease urine flow and sodium excretion, even when RAP was controlled (114 +/- 1 (control) versus 113 +/- 1 mm Hg (NLA+CL)).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Relevance of the tubuloglomerular feedback mechanism in pathophysiology.

The balance between a high filtration rate and high reabsorption rate in the kidney is critical in the maintenance of extracellular fluid volume. One of the mechanisms that maintain this balance is the tubuloglomerular feedback (TGF) mechanism, which operates at the level of the macula densa assessing the load and/or solute concentration coming out of the loop of Henle and controlling this load by adjusting the GFR. This review discusses the potential role of the TGF system with respect to volume homeostasis in various conditions where GFR is maintained, decreased, or increased. In most of the states discussed, the TGF system seems to act appropriately regarding volume control; however, trade-off effects occasionally occur. After acetazolamide administration, during extracellular fluid volume contraction or expansion or acute hyperkalemia, the TGF mechanism responds appropriately with regard to volume balance. After a large reduction of renal mass, the system adjusts to function at a higher level of GFR and distal delivery. In chloride-depletion metabolic alkalosis, glomerulonephritis, diabetes mellitus, and acute renal failure, the adaptation of the TGF system appears to be appropriate with regard to volume control; however, it may lead to trade-off effects, such as maintenance of metabolic alkalosis, glomerular hypertension and sclerosis, or depression of GFR, respectively. Because the TGF mechanism often contributes to compensatory adjustments to or development of disease, it can be appreciated that any in-depth evaluation of the mechanisms responsible for various pathophysiologic conditions should include an assessment of the potential role of the TGF mechanism.

Acute Kidney Injury↗
PubMed1992

Role of endothelium-derived nitric oxide in the renal hemodynamic response to amino acid infusion.

The present study was performed in anesthetized rats to compare the renal hemodynamic responses to mixed amino acids (M-AA) with those to L-arginine (L-Arg) and to examine the effect of endothelium-derived nitric oxide (EDNO) synthesis blockade on the M-AA-induced rise in renal plasma flow (RPF) and glomerular filtration rate (GFR). Intravenous infusion of both M-AA (Ser, Gly, Ala, and Pro, 0.71 mmol.100 g-1.min-1) and L-Arg (0.71 mmol.100 g-1.min-1) increased RPF and GFR. Peak increases in RPF for M-AA and L-Arg were 39.7% (P less than 0.05) and 63.4% (P less than 0.01), whereas GFR increases were 33.6% (P less than 0.05) and 46.7% (P less than 0.01, respectively). Outer cortical blood flow (OCBF) was increased with both treatments. Sodium excretion and urine flow were increased more with L-Arg than M-AA (both P less than 0.01). Infusion of the nitric oxide synthesis inhibitor, nitro-L-arginine (N-L-Arg, 20 micrograms.100 g-1.min-1) increased mean arterial pressure but decreased RPF 48.4% (P less than 0.001), OCBF 39.5% (P less than 0.001), GFR 37.8% (P less than 0.01), urine flow 29.8% (P less than 0.01), and sodium excretion 40.9% (P less than 0.01). When M-AA was administered after N-L-Arg, significant increases in OCBF, RPF, and GFR were observed (P less than 0.01); there was also an enhancement of sodium excretion and urine flow (both P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Angiotensin and angiotensin converting enzyme tissue levels in two-kidney, one clip hypertensive rats.

Renal tissue angiotensin I (Ang I) and II (Ang II) content and angiotensin converting enzyme activity were assessed in both kidneys during initial (7 days) and maintenance (25 days) phases of two-kidney, one clip hypertension in rats. At 7 and 25 days, systolic arterial pressure was 146 +/- 2 and 170 +/- 7 mm Hg, respectively. After 7 days, Ang I content of clipped kidneys was 64% and 70% higher (p < 0.001) than in nonclipped and sham-operated kidneys, respectively, when compared with levels in kidneys from sham-operated rats. In kidneys harvested 25 days after clipping one renal artery, Ang I and Ang II contents in clipped kidneys were increased 102% and 24% (p < 0.01), respectively. Ang II content was also 32% higher in nonclipped kidneys. Angiotensin converting enzyme activity in nonclipped kidneys was greater (p < 0.05) than that in either clipped (46% higher) or sham-operated kidneys (57% higher). Plasma Ang I and Ang II levels were elevated at 7 days but were not different at 25 days in clipped rats. These results demonstrate a dissociation between intrarenal and circulating levels of Ang I and Ang II and suggest that qualitatively different mechanisms may be responsible for the elevated intrarenal Ang II levels during the initial and maintenance phases of renal hypertension.

Angiotensin I↗
PubMed1992

Effects of calcium antagonists on renal hemodynamics and glomerular function.

Cytosolic [Ca2+] can be increased by influx of the ion from the extracellular compartment, Ca2+ release from intracellular storage sites, and/or a reduced activity of active transport processes for Ca2+ extrusion or sequestration. Organic calcium antagonists block transmembrane calcium entry and, therefore, can be utilized to evaluate the importance of calcium influx in the regulation of renal hemodynamics. Recent studies indicate that calcium antagonists selectively vasodilate preglomerular arterioles, leading to increases in renal blood flow (RBF), glomerular filtration rate (GFR) and glomerular pressure. In contrast with angiotensin converting enzyme inhibitors and other vasodilator agents, calcium antagonists primarily influence the component of renal vascular resistance responsible for autoregulation, potently attenuating autoregulatory efficiency. Calcium antagonists also block the afferent arteriolar vasoconstriction elicited by angiotensin II, while not influencing the efferent arteriolar vasoconstriction evoked by this peptide. Tubuloglomerular feedback (TGF)-mediated vasoconstrictor responses are also abolished by calcium antagonists, indicating that the TGF effector mechanism may require transmembrane calcium influx into the smooth muscle cells of the afferent arterioles. These observations provide compelling evidence that calcium influx, through pathways which are influenced by organic calcium antagonists, is an integral component of the afferent arteriolar vasoconstriction elicited by a variety of stimuli, while efferent arteriolar vasoconstriction appears to depend on other calcium access pathways.

Angiotensin II↗
PubMed1991

Synergistic intrarenal actions of angiotensin on tubular reabsorption and renal hemodynamics.

There is a growing awareness that the direct intrarenal actions of angiotensin II (ANG II) on both tubular and vascular structures contribute to sodium conservation. Even very low concentrations of ANG II (10(-1)) mol/L) stimulate proximal reabsorption rate. Recent studies indicate that this stimulatory action is due to an enhanced activity of the sodium/hydrogen exchanger of the luminal membrane. Elevated ANG II levels in the renal interstitium, effected either through increased delivery of ANG II via the circulation or as a consequence of conversion of angiotensin I (ANG I) generated locally, can also enhance proximal reabsorption rate. One consequence of enhanced proximal reabsorption rate is reduced distal volume delivery, which would be expected to elicit arteriolar vasodilation mediated by the tubuloglomerular feedback (TGF) mechanism. It has been observed, however, that peritubular capillary infusions of either ANG I or ANG II, at doses sufficiently low to be without obvious direct effects on glomerular dynamics, can increase the sensitivity of the TGF mechanism. This enhanced TGF sensitivity serves to minimize or prevent TGF mediated increases in glomerular filtration rate in the face of reduced distal delivery. With greater increases in interstitial ANG II concentration, reductions in glomerular pressure have been observed, demonstrating a powerful action on preglomerular arterioles that predominates over the well known effects on efferent arterioles. At these higher doses, the direct hemodynamic actions of ANG II, plus the effects on the glomerular filtration coefficient, will directly reduce filtered sodium load. Through these synergistic effects on both tubular reabsorptive and hemodynamic function, ANG II can elicit sustained decreases in distal nephron sodium delivery which contribute greatly to its efficacy as a regulator of sodium excretion.

Absorption↗
PubMed1990

Absence of glomerular injury or nephron loss in a normotensive rat remnant kidney model.

Severe reduction in renal mass (greater than 50%) in the rat uniformly results in progressive glomerular injury and loss of remnant nephrons postulated to be due to increases in glomerular function (hyperfiltration) and/or size (hypertrophy). Reduction in renal mass in the rat also leads to the development of systemic and/or glomerular hypertension. To examine the independent contributions of systemic hypertension and glomerular hyperfiltration and/or hypertrophy to progressive glomerular injury, a normotensive rat remnant kidney model was developed in the Wistar-Kyoto (WKY) strain. Of the 34 WKY rats that underwent 5/6 nephrectomy, 25 remained normotensive and without evidence of morphologic glomerular injury and/or nephron loss for up to 14 to 16 weeks, despite glomerular hyperfiltration and hypertrophy comparable to that previously observed in other rat strains. Micropuncture studies at approximately six weeks after reduction in renal mass demonstrated markedly increased SNGFR in remnant nephrons of normotensive rats as compared to controls (66 +/- 7 vs. 25 +/- 4 nl/min, P less than 0.01), but glomerular capillary pressures (PGC) estimated from stop flow pressures were only slightly increased (52.7 +/- 1 vs. 47.3 +/- 1 mm Hg, P less than 0.01). These data indicate that compensatory glomerular hyperfiltration and hypertrophy after 5/6 nephrectomy may not lead to progressive glomerular injury provided hypertension does not develop. These data further suggest that in the absence of systemic hypertension, increases in PGC required for adaptive hyperfiltration, may not be sufficient to initiate progressive glomerular injury and nephron loss.

Animals↗
PubMed1990

Application of polar-orbiting, meteorological satellite data to detect flooding of Rift Valley Fever virus vector mosquito habitats in Kenya.

Measurements of green-leaf vegetation dynamics recorded by the advanced very high resolution radiometer instruments onboard National Oceanic and Atmospheric Administration satellites 7 and 9 were used to derive ground moisture and rainfall patterns in Kenya and monitor resultant flooding of mosquito larval habitats (dambos) likely to support Rift Valley Fever virus vector mosquitoes (Aedes and Culex spp.). Satellite-derived data from mid-1981 to December 1988 have been analysed with corresponding rainfall, flooding and vector population data as they relate to Rift Valley Fever virus ecology. Single (7 x 7 km) and multiple grid-cell image analysis (200 x 300 km) in small localized areas and large geographical regions, respectively, of vegetation data were used to quantify the potential for flooding of mosquito breeding habitats. The ability to detect accurately parameters, such as ground moisture, that determine flooding could provide local officials with sufficient warning to allow for implementation of specific mosquito control measures before a disease outbreak.

Animals↗
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↗