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T H Steele

Publications and source records attributed to T H Steele.

At least 19 recordsLinked to original sources
PubMed1990

Intrarenal angiotensin II inhibition influences the actions of atrial natriuretic peptide.

1. We previously found that kidneys isolated from salt-restricted rats were refractory to atrial natriuretic peptide compared with kidneys from salt-loaded rats. Because the intrarenal tissue renin-angiotensin system may modulate renal responses to atrial natriuretic peptide, we examined the effect of dietary NaCl loading on the responses of isolated perfused kidneys from normal rats to atrial natriuretic peptide, before and after the addition of angiotensin II receptor antagonists or angiotensin I converting enzyme inhibitors to the perfusate. 2. Atrial natriuretic peptide increased the glomerular filtration rate and sodium excretion of kidneys from NaCl-loaded rats. The addition of angiotensin receptor antagonists or converting enzyme inhibitors partially reversed the increments in glomerular filtration rate but not the increments in sodium excretion, leading to an increased fractional sodium excretion. In the absence of atrial natriuretic peptide, these agents did not affect glomerular filtration or sodium excretion. Kidneys from NaCl-restricted rats did not respond to atrial natriuretic peptide or to the inhibitors and antagonists, either separately or in combination. 3. After NaCl loading, the intrarenal renin-angiotensin system may augment the glomerular response to atrial natriuretic peptide while simultaneously inhibiting the natriuretic response to atrial natriuretic peptide. However, activation of the intrarenal renin-angiotensin system is not responsible for the refractoriness of kidneys from salt-restricted rats to atrial natriuretic peptide.

Angiotensin II↗
PubMed1988

Function of the hypertensive kidney during calcium flux manipulation.

Dihydropyridine calcium channel agonists and antagonists elicit exaggerated glomerular and circulatory responses from kidneys isolated from Dahl rats genetically programmed to develop NaCl-induced hypertension (Dahl S rats). These differential responses are further magnified by NaCl loading. In contrast, "chemical sympathectomy" with 6-hydroxydopamine enhances renal vascular responses to calcium channel agonists in a manner that depends on the antecedent dietary NaCl intake, and is independent of genetic predilection to develop NaCl-induced hypertension. These findings are consistent with the hypothesis that aberrations of vascular and perhaps glomerular calcium entry modulation may be determinants of altered renal hemodynamics in NaCl-sensitive hypertension. The latter may be responsible for the enhanced responsiveness to calcium channel antagonists observed in NaCl-sensitive hypertension in humans.

Animals↗
PubMed1988

Increased vascular response to calcium channel agonist by Dahl S rat kidney.

We examined responses to the calcium channel agonist, BAY-K 8644, of isolated perfused kidneys from Dahl salt-sensitive (DS) and -resistant (DR) rats that had been stabilized on high (HI) and low (LO) NaCl intakes. Mean arterial pressures of DS/HI rats exceeded those of the other three groups. BAY-K 8644 significantly increased the renal vascular resistance (RVR) of DS/HI and DS/LO kidneys, by 38 and 12%, respectively, but did not increase RVR of DR/HI or DR/LO kidneys significantly (6 and 2%, respectively). Increases in RVR and decreases in glomerular filtration rate of DS/HI kidneys exceeded those of DR/HI kidneys. Increases in the RVR of DS/LO kidneys exceeded those of DR/LO kidneys. Experiments utilizing the separate calcium channel agonist and antagonist enantiomers of BAY-K 8644 corroborated these findings, but at lower concentrations. "Chemical sympathectomy" with 6-hydroxydopamine increased the reactivity of kidneys from only high-NaCl animals to BAY-K 8644 without regard to Dahl S or R status. In conclusion, the DS kidney vasculature manifests an increase in responsiveness to this calcium channel agonist, independently of antecedent NaCl loading or high blood pressure. However, a high antecedent salt intake or hypertension enhances vascular responsiveness of the DS kidney to BAY-K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Genetics and salt modulate renal responses to atrial natriuretic factor.

We examined the consequences of genetic susceptibility or resistance to NaCl-induced hypertension and of prior salt loading (high or low NaCl intake) on the responses of isolated perfused Dahl salt-sensitive (DS) and Dahl salt-resistant rat (DR) kidneys to atriopeptin II. Atriopeptin II increased the glomerular filtration rate only in kidneys from high NaCl-fed rats, irrespective of their DS or DR status. Superimposition of norepinephrine on atriopeptin II further increased the glomerular filtration rate only in kidneys from low NaCl-fed rats (which had not reacted to atriopeptin II alone), irrespective of their DS or DR status, and did not change the glomerular filtration rate of high NaCl-fed rats. Norepinephrine alone, without atriopeptin II, uniformly decreased the glomerular filtration rate by about 80%. Atriopeptin II increased sodium excretion of high NaCl and low NaCl DR kidneys by more than five times as much as in the corresponding DS kidneys. Therefore, the glomerular filtration rate response to atriopeptin II varied globally with dietary NaCl, independently of genetic predisposition or resistance to NaCl-induced hypertension. The natriuretic response to atriopeptin II was blunted in kidneys from rats genetically susceptible to NaCl-induced hypertension, independently of their NaCl consumption. Atriopeptin II also ameliorated or reversed the adverse effect of norepinephrine on the glomerular filtration rate.

Animals↗
PubMed1987

Response of isolated Dahl rat kidney to calcium antagonists.

We studied the responses of isolated perfused kidneys from prehypertensive, salt-sensitive (DS) and salt-resistant (DR) Dahl rats to nitrendipine or verapamil, after norepinephrine vasoconstriction. The perfusion pressure was kept constant. Superimposition of these calcium antagonists upon norepinephrine increased DS GFR by 155% and DR GFR by 58% (P = 0.03), with verapamil increasing the GFR more than nitrendipine (P = 0.02). Nitrendipine and verapamil also partially reversed norepinephrine induced increases in renal vascular resistance, but did not decrease vascular resistance or increase GFR in the absence of norepinephrine. During the increase in GFR produced by calcium antagonists, DR sodium excretion increased, but DS sodium excretion did not. Therefore, calcium antagonists disproportionately increased DS kidney GFR but did not correct DS kidney sodium retention. These data raise the possibility that the DS rat kidney possesses an abnormality of cell calcium regulation affecting glomerular dynamics, and provide evidence that the renal perfusion pressure is more critical than the GFR in adjusting DS rat sodium-excretion.

Animals↗
PubMed1987

Influence of salt on response to nitrendipine by Dahl rat kidney.

We examined the responses to the calcium channel blocker, nitrendipine, of isolated perfused kidneys from Dahl salt-sensitive (DS) and salt-resistant (DR) rats that had been stabilized on high- and low-NaCl diets. Blood pressures of high-salt DS rats exceeded those of the other three groups. After norepinephrine vasoconstriction sufficient to increase renal vascular resistance (RVR) by 50%, the superimposition of 10(-5) M nitrendipine increased the glomerular filtration rate (GFR) of high-salt DS rat kidneys by 125% over control values but returned the GFR of high-salt DR kidneys only to control. Nitrendipine superimposition increased the GFR of low-salt DS and DR rat kidneys by 124 and 40% over control values, respectively, and partially restored the RVR toward control. Nitrendipine alone, without norepinephrine, did not affect the GFR or RVR. The persistence within the DS kidney of an exaggerated glomerular circulatory "rebound" response to nitrendipine following the development of hypertension suggests the possibility of a maladaptation of DS kidney cell calcium regulation. The DR kidney manifests a similar response during salt restriction, but this disappears on a high-NaCl diet.

Animals↗
PubMed1987

Calcium entry modulation and renal hemodynamics in the hypertensive kidney.

In the isolated perfused rat kidney, the superimposition of a number of calcium entry blockers (CEB) upon norepinephrine vasoconstriction prompts an increase in the glomerular filtration rate (GFR) to a level substantially greater than the original value. A similar acute GFR response to CEB is manifested in the intact anesthetized rat with the renal perfusion pressure remaining constant. This glomerular response to CEB is accentuated in isolated perfused kidneys from Dahl salt-sensitive (DS) rats as compared with kidneys from Dahl salt-resistant (DR) rats. The disparities between DS and DR kidney responses are further amplified in the DS rat kidney after a high NaCl intake and the development of hypertension by the DS rat. In addition, vasoconstrictor responses to BAY-K 8644, a calcium entry facilitator, are accentuated in DS rat kidneys, and even more so following a high NaCl intake or 'chemical sympathectomy' with 6-hydroxydopamine. These results suggest that subtle changes in vascular and glomerular calcium entry modulation may be the key determinants of altered renal hemodynamics in salt-dependent hypertension.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Dihydropyridine calcium antagonists and agonists in the isolated perfused Dahl rat kidney.

Isolated perfused kidneys from prehypertensive Dahl salt-sensitive (DS) rats demonstrated marginally increased glomerular responsiveness when nitrendipine or verapamil was superimposed upon norepinephrine vasoconstriction. This was manifested by a greater increase in the glomerular filtration rate of DS rat kidneys, as compared to kidneys from Dahl salt-resistant (DR) rats. This glomerular response to nitrendipine by isolated kidneys was not affected by the development of salt-induced hypertension in DS rats, but was eliminated by antecedent salt loading in DR rats. In further experiments designed to assess more directly the reactivity of renal vascular calcium channels in DS and DR rats, the calcium channel agonist BAY-K-8644 and its pure agonist isomer elicited greater increases in renal vascular resistance in kidneys from prehypertensive DS rats than in kidneys from similarly prepared DR rats. Renal vascular reactivity to both BAY-K-8644 and its agonist isomer were greatly magnified following salt-induced DS rat hypertension. These results suggest that a genetically conferred abnormality of calcium channel function may contribute to the renal functional characteristics of the DS rat kidney.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Exaggerated Dahl salt-sensitive kidney response to calcium channel agonist isomer of Bay k 8644, but not to calcium channel antagonist isomer of Bay k 8644.

We examined the influence of calcium channel agonist and antagonist optical isomers of BAY-K-8644 on the renal vascular resistance, glomerular filtration rate and sodium excretion of isolated perfused kidneys from Dahl salt-sensitive (DS) and salt-resistance (DR) rats previously stabilized on high- and low-NaCl regimens. The agonist isomer affected these parameters at a lower concentration and to a greater degree in the high-salt DS rat kidneys than in the other three groups. The antagonist isomer also reversed agonist-induced changes to the greatest degree in the high-salt DS rat kidneys. However, the low-salt DS and high-salt DR rat kidneys appeared to be slightly more reactive to these isomers than the low-salt DR rat kidneys, suggesting that hereditary predisposition and dietary NaCl may contribute independently to renal responsiveness to calcium channel-active agents.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Glomerular response to verapamil by isolated spontaneously hypertensive rat kidney.

We investigated the possibility that altered cell calcium regulation may affect function of isolated Kyoto spontaneously hypertensive rat (SHR) kidneys as compared with kidneys from Wistar-Kyoto control (WKY) rats. The kidneys were perfused at 120 and 160 mmHg. At 120 mmHg, SHR glomerular filtration rate (GFR) was 0.24 +/- 0.04 compared with WKY GFR of 0.70 +/- 0.10 ml/min (P = 0.001). At 160 mmHg, SHR GFR was 0.48 +/- 0.05 compared with WKY GFR of 1.09 +/- 0.05 ml/min (P less than 0.001). At 120 mmHg, addition of norepinephrine increased renal vascular resistance (RVR) by 50% and decreased SHR GFR by 27% and WKY GFR by 57% (P = 0.04). At 160 mmHg, norepinephrine elicited similar changes. Addition of verapamil, 5-10 microM, in the presence of norepinephrine returned RVR to 100-110% of control. With verapamil at 120 mmHg, SHR GFR increased to 0.84 +/- 0.23 ml/min, a value 3.5 times that of control (P = 0.03). In contrast, WKY GFR in the presence of norepinephrine and verapamil was 0.97 +/- 0.07 ml/min, unchanged from control (P = 0.07). At 160 mmHg, norepinephrine and verapamil also failed to increase WKY GFR above control (P = 0.4) but increased SHR GFR to 52% above control (P = 0.03). Isolated SHR kidneys exhibited exaggerated GFR responses to verapamil but not to norepinephrine. Abnormal cell calcium regulation may underlie the marked decrease in GFR when SHR kidneys are perfused acutely at normotensive perfusion pressures.

Animals↗
PubMed1985

Function of the isolated spontaneously hypertensive rat kidney after blood pressure reduction.

We treated 20-week-old spontaneously hypertensive rats (SHR) with either placebo or hydralazine, reserpine and hydrochlorothiazide for 1 month. Mean arterial pressure in treated SHR averaged 113 +/- 7 mm Hg (mean +/- SE), compared to 162 +/- 12 mm Hg in animals receiving placebo (p less than 0.01). Glomerular filtration rate (GFR) and sodium excretion were similar in both groups. In isolated perfused kidneys, the GFR and sodium excretion were significantly greater in the treatment group than in the placebo group at a perfusion pressure of 140 mm Hg (p less than 0.01). Renal vascular resistance (RVR) of kidney from treated SHR was no different from RVR of kidney from placebo SHR. Hydralazine (6 mM) and diazoxide (4 mM) increased the GFR and sodium excretion of isolated SHR kidney perfused at 140 mm Hg (p less than 0.05), but decreased RVR significantly (p less than 0.05). We conclude that prolonged antihypertensive treatment renders higher GFR values to isolated SHR kidneys perfused at 140 mm Hg, with sodium excretion varying in proportion to the GFR. The addition of vasodilators to the perfusate of isolated SHR kidneys partially reproduced these changes, but only at extremely high concentrations unlike to be attained in vivo.

Animals↗
PubMed1985

Muzolimine modification of renal vasoconstriction.

Utilizing an isolated perfused rat kidney preparation, we studied the modification by muzolimine of changes in glomerular filtration rate (GFR) and renal vascular resistance (RVR). Superimposition of muzolimine upon norepinephrine-induced vasoconstriction revealed that muzolimine returned RVR nearly to control values and increased GFR to supracontrol values. Muzolimine reversed norepinephrine-induced decreases in GFR at concentrations as low as 1 microM, but reduced RVR only at concentrations of 500 microM or greater. Muzolimine also reversed, at least partially, the increased RVR and depressed GFR secondary to potassium-induced depolarization. Although muzolimine has not been shown to possess calcium antagonist activity, our data inicate that it elicits renal actions similar to calcium channel blockers at high concentrations. It also elicits a specific increase in GFR during intense norepinephrine-induced vasoconstriction.

Animals↗
PubMed1979

Hypouricemia.

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Body Water↗
PubMed1979

Mechanism of the uricosuric activity of ticrynafen.

Studies employing pyrazinamide, which have included the measurements of clearances of pyrazinamide and pyrazinoate, as well as of ticrynafen itself and its principal metabolite, have lent support to the hypothesis that ticrynafen inhibits the tubular reabsorption of both filtered and secreted urate by nephrons of the human kidney. The inhibition of the reabsorption of secreted urate by ticrynafen appears to be quantitatively important for eliciting its uricosuric and hypouricemic responses. Because the uricosuric and natriuretic responses correlate with urinary ticrynafen concentrations, the drug appears to inhibit tubular reabsorption after gaining access to tubule fluid. As a consequence of its extensive binding to plasma proteins, clearance data suggest that tubular secretion of ticrynafen is necessary for its action.

Diuretics↗
PubMed1979

Renal handling of urate: application to the action of tienilic acid.

The renal handling of urate is complex, involving its filtration by glomeruli, partial tubular reabsorption, tubular secretion and also the reabsorption of a portion of the secreted urate. Studies employing tienilic acid, both acutely and chronically, have suggested that this compound exerts its uricosuric action and decreases the plasma urate by inhibiting renal urate reabsorption. The magnitude of the natriuretic and uricosuric actions of tienilic acid are correlated with the concentration of drug in the urine. Crystal equilibration studies have suggested that tienilic acid should not predispose to crystalluria with either uric acid or monosodium urate.

Animals↗