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R Loutzenhiser

Publications and source records attributed to R Loutzenhiser.

At least 37 records · Page 2Linked to original sources
PubMed1991

Direct studies on the control of the renal microcirculation.

Recent advances in videomicroscopy combined with the development of several innovative in vivo and in vitro preparations now allow for direct study of the renal microcirculation. Blood flow in vasa recta capillaries of the rat can be studied by using video-microscopy, and changes in the flow of red blood cells in the renal cortex and papilla can be continuously monitored by using laser-Doppler flowmetry. All elements of the renal microcirculation can be visualized with the in vitro perfused juxtamedullary nephron or hydronephrotic kidney preparations. Pressures, blood flows, and vascular diameters in individual vessels can be directly measured in these preparations. Renal arterioles can be microdissected from the kidneys of several species and cannulated and pressurized in vitro for the study of pressure-diameter relationships and vascular responses to different agonists. In addition, membrane potentials and intracellular ion concentrations can now be measured in isolated renal arterioles by using microelectrodes and fluorescence microscopy. Thus, it is possible to study the control of renal vascular tone at all levels of integration from signal transduction in isolated cells to direct analysis of the regulation of hemodynamics in different regions of the microcirculation of the kidney in intact animals.

Animals↗
PubMed1990

Direct visualization of effects of endothelin on the renal microvasculature.

The renal microvascular and hemodynamic actions of endothelin were assessed directly in isolated perfused hydronephrotic (HYD) and normal kidneys, respectively. In HYD kidneys endothelin was a potent vasoconstrictor of the afferent arteriole (AA), eliciting a threshold vasoconstrictor response at 0.01 nM (P less than 0.05). At 0.1 and 0.3 nM, endothelin reduced AA diameter by 22 +/- 6 (P less than 0.025) and 41 +/- 4% (P less than 0.001), respectively. Furthermore, endothelin provoked oscillatory vasomotion in the AA. In contrast, endothelin had less effect on the efferent arteriole (EA), reducing EA diameter by only 7 +/- 4 (P greater than 0.20) and 13 +/- 4% (P less than 0.05), at 0.1 and 0.3 nM, respectively. In normal kidneys endothelin elicited a long-lasting vasoconstriction with a dose dependency similar to that observed in the AA of HYD kidneys. Furthermore, endothelin reduced glomerular filtration rate (GFR) from 0.58 +/- 0.04 to 0.09 +/- 0.05 ml.min-1.g-1 (P less than 0.001) in this model. Both the AA vasoconstriction and reduction in GFR were completely reversed by nifedipine. These findings indicate that endothelin is a potent renal vasoconstrictor that decreases GFR by a predominant vasoconstriction of the AA. Our observations are consistent with the postulate that endothelin elicits renal vasoconstriction via a mechanism involving dihydropyridine-sensitive calcium channels and that such calcium channels play a prominent role in the activation of the AA.

Animals↗
PubMed1990

Determinants of renal actions of atrial natriuretic peptide. Lack of effect of atrial natriuretic peptide on pressure-induced vasoconstriction.

We have previously demonstrated that atrial natriuretic peptide (ANP) completely reverses norepinephrine-induced afferent arteriolar (AA) vasoconstriction. In the present study we characterized the effects of ANP on pressure-induced vasoconstriction of AA. Chronic unilateral hydronephrosis was induced to facilitate direct visualization of the renal microcirculation. Hydronephrotic kidneys were perfused in vitro, and AA diameters were measured during stepwise alterations in renal arterial pressure. Increasing renal arterial pressure from 80 to 180 mm Hg decreased AA diameter by 22 +/- 2% (from 18.5 +/- 1.0 to 14.4 +/- 1.0 microns, p less than 0.005). In the presence of 100 nM ANP [human ANP-(4-28)], AA vasoconstricted by 23 +/- 4%, indicating that ANP failed to modify the pressure-induced AA vasoconstriction. Furthermore, both nitroprusside (10 microM) and 8-bromoguanosine 3':5'-cyclic monophosphate (30 microM) only partially inhibited pressure-induced AA vasoconstriction (31 +/- 5% and 47 +/- 7%, respectively), whereas these vasodilators completely abolished norepinephrine-induced AA vasoconstriction. In contrast, nifedipine completely inhibited pressure-induced AA vasoconstriction. In summary, pressure-induced AA vasoconstriction is insensitive to the action of ANP, is relatively refractory to cyclic GMP-mediated vasorelaxation, but is completely inhibited by calcium channel blockade. Furthermore, since ANP completely abolishes norepinephrine-induced vasoconstriction but fails to affect pressure-induced vasoconstriction, it is apparent that the type of underlying vasoconstrictor stimuli constitutes a major determinant of the renal microvascular response to ANP.

Animals↗
PubMed1990

H(+)-induced vasodilation of rat aorta is mediated by alterations in intracellular calcium sequestration.

Acidosis induces vasodilation both in vivo and in vitro. Although it is commonly surmised that acidosis alters contractility by affecting contractile proteins and calcium entry, the exact role of these mechanisms in acidosis-induced vasodilation has not been determined. In the present study, we demonstrated that a novel mechanism, involving increased calcium sequestration into intracellular sites sensitive to norepinephrine, mediates the vasodilation associated with relatively modest decreases in pH. The effects of changing pH from 7.4 to 7.0 on tension development, 45Ca fluxes, and the norepinephrine-releasable intracellular calcium stores were studied in isolated rat aorta. Acute acidification produced marked endothelium-independent dilations of aortic rings that had been precontracted with norepinephrine. In contrast, this maneuver had only modest effects on contractions elicited by 80 mM KCl or phorbol ester. Acidification in this range did not alter basal or norepinephrine-stimulated undirectional 45Ca influx, nor did it reduce the norepinephrine-induced net gain in 45Ca content. Furthermore, neither norepinephrine-stimulated 45Ca efflux nor the peak contractile response to norepinephrine in calcium-free buffer was affected, although in this setting, the duration of the phasic contractile response was shortened. When calcium was restored to tissues exposed to norepinephrine in calcium-free buffer, acidification slowed the rate of tension development without altering 45Ca uptake, thus changing the relation between tension development and calcium entry. These effects of acidification were shown to be associated with an increase in the amount of calcium sequestered into the norepinephrine-sensitive intracellular calcium store. These findings clearly indicate that acidification, within a range that has no effect on other aspects of smooth muscle activation, elicits vasodilation by stimulating intracellular calcium sequestration. This action may represent a predominant mechanism whereby acidosis alters vascular smooth muscle contractility.

Acetylcholine↗
PubMed1990

Renal microvascular actions of calcium antagonists.

Calcium antagonists elicit vasodilation by altering the function of a specific class of potential-dependent calcium channels. These agents alter renal hemodynamics in a complex manner. Studies in the isolated perfused rat kidney demonstrate that the renal vasodilatory response to calcium antagonists varies depending on the nature of the underlying renal vasoconstriction. Thus, not all renal vasoconstrictor mechanisms are sensitive to calcium antagonists. Furthermore, in the presence of agonists such as norepinephrine or angiotensin II, calcium antagonists exert a greater effect on glomerular filtration rate than on renal perfusate flow. Direct observations of the renal microvasculature suggest that this preferential augmentation of glomerular filtration rate reflects the ability of calcium antagonists to dilate preglomerular vessels while preserving efferent arteriolar tone. Thus, under identical in vitro conditions, calcium antagonists reverse afferent (preglomerular) but not efferent (postglomerular) arteriolar vasoconstriction in isolated perfused hydronephrotic kidneys. Similarly, potassium (KCl)-induced depolarization, which directly activates potential-dependent calcium channels, preferentially constricts the afferent arteriole and produces a striking decrease in glomerular filtration rate and filtration fraction. Such observations indicate that differing activating mechanisms mediate vasoconstriction within the renal microcirculation and suggest that potential-dependent calcium channels prominently contribute to afferent, but not efferent, arteriolar vasoconstriction.

Angiotensin II↗
PubMed1989

Divergent effects of KCl-induced depolarization on afferent and efferent arterioles.

We have previously proposed that renal microvessels exhibit a unique regional heterogeneity. Studies with calcium channel agonists and antagonists suggest that potential-dependent calcium channels may play a more prominent role in the activation of the afferent arteriole than the efferent arteriole. Because KCl-induced depolarization elicits vasoconstriction exclusively by the activation of potential-dependent calcium channels, we tested this postulate directly by ascertaining the vasoconstrictor effects of KCl and countervailing effects of a calcium channel blocker on the afferent and efferent arteriole of isolated perfused hydronephrotic kidneys. Increasing media potassium concentration from 5 to 30 mM resulted in a marked renal vasoconstriction decreasing renal perfusate flow by 61 +/- 4%. An examination of the microvascular response to KCl revealed a predominant response of the afferent arteriole. Thus afferent arteriolar diameter decreased by 38 +/- 6% (i.e., from 20.7 +/- 1.5 to 13.0 +/- 1.8 microns, P less than 0.005), whereas efferent arteriolar diameter decreased by only 12 +/- 4% (i.e., from 15.8 +/- 1.6 to 13.8 +/- 1.4 microns, P = 0.05). Nifedipine completely returned afferent arteriolar diameter to control levels with a mean effective dose of 41 +/- 2 nM. These findings indicate that the afferent arteriole is more responsive to depolarization-induced vasoconstrictor stimuli than is the efferent arteriole and suggest a greater prevalence of potential-dependent calcium channels in this vessel.

Animals↗
PubMed1989

Effects of water immersion on atrial natriuretic peptide release in humans.

Water immersion (WI) to the neck induces prompt increases in central blood volume, central venous pressure, and atrial distension. Since atrial distension is a major stimulus for atrial natriuretic peptide (ANP) release, WI constitutes a unique model to investigate the physiological importance of ANP in humans. All studies to date demonstrate that ANP increases during the 1st h of WI in hydrated subjects, rising 2.5- to 3-fold by the end of the 2nd or 3rd h. During recovery from WI, ANP returns promptly to prestudy levels. Although distension of the atria probably constitutes the major stimulus for ANP release during WI, other mechanisms may coexist. In normal hydrated subjects undergoing WI, the increases in ANP correlate with the magnitude of the natriuresis, suggesting that ANP constitutes an important determinant of renal sodium handling in humans. It is simplistic, however, to consider the WI-induced augmentation of ANP to be the sole, or even the prepotent, mediator of the resultant natriuresis. Rather ANP should be considered as one of several hormonal, neural, and hemodynamic factors acting in concert in an integrated matrix to modulate volume homeostasis. Clearly, the results of several recent studies utilizing WI demonstrate that this maneuver constitutes an important investigative model to delineate further the role of ANP in subserving volume homeostasis in normal humans and in disorders of deranged volume regulation.

Animals↗
PubMed1989

Relationship between plasma ANF responsiveness and renal sodium handling in cirrhotic humans.

The responsiveness of atrial natriuretic factor (ANF) to central volume expansion and its role as a determinant of the natriuretic and diuretic responses of cirrhotic patients was evaluated utilizing water immersion (WI). Following equilibration on a 10-mEq sodium diet, 9 seated cirrhotic patients were studied during 3 h of WI. Before WI, plasma ANF levels (10.9 +/- 2.4 fmol/ml) were similar to those previously observed in normal sodium-replete subjects (7.7 +/- 0.9 fmol/ml). Five of the 9 cirrhotic subjects manifested an exaggerated peak ANF response, whereas the remaining 4 manifested increases similar to those of normals. The concomitant natriuretic response varied widely, ranging from absent to markedly exaggerated responses. The peak urinary sodium excretion varied independently of peak plasma levels of ANF and peak change of ANF from the prestudy hour (r = 0.36, p greater than 0.20, and r = 0.46, p greater than 0.20, respectively). Thus, in contrast to normal subjects, in whom the immersion-induced natriuresis correlated closely with the changes in ANF, the natriuretic responses of cirrhotic patients were dissociated from the concomitant increases in ANF. These observations indicate that sodium retention in cirrhosis is not attributable to impaired ANF release.

Adult↗
PubMed1989

Pressure-induced vasoconstriction of renal microvessels in normotensive and hypertensive rats. Studies in the isolated perfused hydronephrotic kidney.

The capacity of small arteries to respond to increased intravascular pressure may be altered in hypertension. In the kidney, hypertension is associated with a compensatory shift in the autoregulatory response to pressure. To directly determine the effects of established hypertension on the renal microvascular response to changes of perfusion pressure, we evaluated pressure-induced vasoconstriction in hydronephrotic kidneys isolated from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Vessel diameters of interlobular arteries (ILAs) and afferent and efferent arterioles were determined by computer-assisted videomicroscopy during alterations in renal arterial pressure (RAP) from 80 to 180 mm Hg. Increased RAP induced a pressure-dependent vasoconstriction in preglomerular vessels (afferent arterioles and ILAs), but not in postglomerular vessels (efferent arterioles). The calcium antagonist nifedipine prevented pressure-induced afferent arteriolar vasoconstriction with a similar half-maximal inhibitory concentration (IC50) (WKY, 63 +/- 27 vs. SHR, 60 +/- 32 nM). The pressure-activation curves for ILAs in SHR and WKY were similar. In contrast, the pressure-activation curve for afferent arterioles in SHR kidneys exhibited a rightward shift, which was observed at every segment of the afferent arteriole (i.e., near ILA, at midportion, and near glomerulus). These findings demonstrate that the ILA and the afferent arteriole both possess the ability to constrict in response to increased pressure, whereas this property is lacking in the efferent arteriole. Hypertension was associated with a compensatory shift in the pressure response of the afferent arteriole, such that higher RAPs were required to elicit vasoconstriction in this vessel.

Animals↗
PubMed1988

Calcium antagonists and the renal hemodynamic response to vasoconstrictors.

These findings demonstrate that calcium antagonists reverse renal vasoconstriction in a variety of settings. The ability of calcium antagonists to augment GFR of the vasoconstricted kidney is striking and has also been demonstrated in a number of in vivo settings. These observations and others raise the possibility that calcium antagonists have potential utility in the treatment of a number of disorders characterized by renal ischemia and consequent renal insufficiency. Further studies to evaluate this possibility are required. The unique effects of calcium antagonists on GFR reflect a regional heterogeneity within the renal microcirculation and a preferential action of calcium antagonists on the afferent arteriole. Final resolution of the pharmacological basis for the renal hemodynamic actions of calcium antagonists will require a more complete understanding of the divergent activating mechanisms within the renal microcirculation.

Animals↗
PubMed1988

Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney.

The intrarenal sites of action of atrial natriuretic peptide (ANP) have not been resolved fully. Although ANP relaxes in vitro preparations of smooth muscle and exerts profound effects on renal hemodynamics, the effects of ANP on resistance vessels remain a subject of controversy. In the present study, we utilized an in vitro perfused hydronephrotic rat kidney model to assess directly the actions of ANP on renal microvessels during norepinephrine (NE)-induced renal vasoconstriction. Perfusion pressure was maintained constant, and perfusate flow to the kidney was monitored while the afferent arteriole (AA) and efferent arteriole (EA) were visualized using videomicroscopy. Renal AA and EA diameters were measured by computer-assisted image analysis. NE (0.3 microM) decreased renal perfusate flow from 11.8 +/- 1.7 (S.E.) to 5.8 +/- 1.2 ml/min (P less than .005), decreased AA diameter from 20.2 +/- 0.7 to 14.3 +/- 0.8 mu (P less than .005) and decreased EA diameter from 18.6 +/- 1.2 to 15.1 +/- 1.2 mu (P less than .005). ANP (human ANF-(4-28), anaritide, Wyeth) completely reversed the NE-induced AA vasoconstriction with an IC50 of 9.3 +/- 5.6 nM. In contrast, ANP caused a further decrease in EA diameter at concentrations up to 10(-8) M, and elicited a slight dilation of the EA at 10(-7) M. In normal rat kidneys perfused under identical conditions, NE decreased renal perfusate flow, glomerular filtration rate and filtration fraction. ANP increased glomerular filtration rate and filtration fraction above control levels, with maximal effects at 10(-8) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Inhibition by diltiazem of pressure-induced afferent vasoconstriction in the isolated perfused rat kidney.

The renal hemodynamic response to calcium entry blockade depends on the neural, hormonal and physiologic determinants influencing basal renal vascular tone. The effects of perfusion pressure per se on the renal vascular response of the rat kidney to diltiazem were evaluated using normal kidneys and hydronephrotic kidneys perfused extracorporally. In isolated perfused normal kidneys, diltiazem did not alter perfusate flow or glomerular filtration rate (GFR) when administered at a perfusion pressure of 100 mm Hg. In contrast, when diltiazem was administered at a perfusion pressure of 150 mm Hg, the calcium antagonists caused a striking increase in GFR, which was accompanied by an increase in renal perfusate flow. In the isolated perfused hydronephrotic rat kidney, elevation of perfusion pressure was associated with an increase in renal vascular resistance and a reduction in afferent arteriolar diameter. Diltiazem abolished the pressure-induced constriction of afferent arterioles and caused an increase in renal perfusate flow in hydronephrotic kidneys perfused at pressures above 100 mm Hg. These findings suggest that in the setting of increased renal perfusion pressure, diltiazem's effects on GFR are mediated in part by an inhibition of pressure-induced constriction of the afferent arteriole.

Animals↗
PubMed1987

Detailed characterization of a tank used for head-out water immersion in humans.

Water immersion has long been known to produce marked diuresis, natriuresis, and kaliuresis and suppression of the renin-aldosterone system. These effects are mediated primarily by an increase in central blood volume. Immersion has therefore gained increased acceptance in human physiology for the investigation of the effects of central volume expansion on renal function and hormonal responsiveness without altering the composition of the extracellular fluid. An immersion tank used for studies in humans is described. Requisite features to ensure study reproducibility include a constant temperature, capability to alter the depth of immersion by adjusting water height, and the ability to maintain hygienic quality by means of constant circulation of the water through a sand filter. A constant temperature of 34.5 +/- 0.2 degrees C is maintained by thermostatically controlling the heat exchange to a unidirectional closed-circuit water system in the bottom of the immersion tank coursing through a stream source. The level of the water may be adjusted to any desired level by means of a waste line or an inlet of tap water.

Equipment Design↗
PubMed1987

Modification of the renal hemodynamic response to vasoconstrictors by calcium antagonists.

Theoretical considerations suggest that the renal response to calcium antagonists may vary depending on the factors influencing basal vascular tone. Studies were conducted using the isolated perfused rat kidney to determine the response to calcium antagonists under conditions in which the determinants of renal vascular tone were accurately defined. With this model, calcium antagonists elicit vasodilation only in the presence of a vasoconstrictor. In this setting, however, the degree of vasodilation elicited depends on the nature of the vasoconstrictor employed. Thus, the reduction in renal perfusate flow (RPF) elicited by KCl-induced depolarization was completely reversed by the calcium antagonist, nitrendipine. In contrast, identical levels of vasoconstriction elicited by norepinephrine or angiotensin II were only partially reversed, suggesting that these agonists activate the renal vasculature by mechanisms that are more complex than membrane depolarization. Examination of the response of glomerular filtration rate (GFR) revealed that in the presence of norepinephrine and angiotensin II, nitrendipine exerted a preferential augmentation of GFR. Thus, concentrations that produced only modest effects on RPF increased GFR to levels equal to or exceeding control values. This selective augmentation of GFR did not occur during the renal vasoconstriction elicited by KCl. It is proposed that renal microvessels exhibit regional heterogeneity in regard to activation mechanisms and sensitivity to calcium antagonists. Calcium antagonists may selectively attenuate agonist-induced vasoconstriction of preglomerular vessels.

Animals↗
PubMed1987

Relationship of increased plasma atrial natriuretic factor and renal sodium handling during immersion-induced central hypervolemia in normal humans.

Although maneuvers augmenting atrial volume and/or stretch also augment plasma levels of atrial natriuretic factor (ANF), the role of ANF in modulating renal sodium and water handling has not been defined. Water immersion to the neck (NI) was employed to assess the ANF response to acute volume expansion in 13 seated sodium-replete normal subjects. ANF increased promptly and markedly from 7.8 +/- 1.8 to 19.4 +/- 3.8 fmol/ml, then declined to 6.3 +/- 1.4 fmol/ml after 60 min recovery. Concomitantly, NI increased urine flow rate (V) (2.0 +/- 0.6 to 7.0 +/- 0.9 ml/min; P less than 0.001) and sodium excretion (UNaV) (92 +/- 12 to 191 +/- 15 mu eq/min; P less than 0.001), and decreased PRA (-66 +/- 3%) and plasma aldosterone (-57 +/- 6%). Increases of plasma ANF ranged from less than 20% to over 12-fold. Similarly, the natriuretic response to NI varied markedly from none to 500%. There was a strong correlation between peak ANF and peak UNaV (r = 0.67; P less than 0.025), but none between peak V and peak plasma ANF (r = -0.10; P greater than 0.5). These findings suggest that an increase in plasma ANF contributes to the natriuretic response to NI, implying a physiological role for ANF in modulating volume homeostasis in humans.

Adult↗
PubMed1987

Modification by dihydropyridine-type calcium antagonists of the renal hemodynamic response to vasoconstrictors.

The effects of dihydropyridines on the renal response to vasoconstrictors was assessed using the isolated perfused rat kidney. During norepinephrine-induced vasoconstriction, dihydropyridines preferentially alter glomerular filtration rate and have less of an effect on perfusate flow. Calcium channel antagonists such as nitrendipine and nisoldipine augment glomerular filtration rate, whereas calcium channel agonists depress glomerular filtration rate. A preferential effect on glomerular filtration rate is also observed with the administration of nitrendipine to kidneys during vasoconstriction induced by angiotensin II. In contrast, nitrendipine does not exert a preferential augmentation of glomerular filtration during vasoconstriction mediated by KCl-induced depolarization. These observations are discussed in the context of the cellular mechanisms of dihydropyridines. It is proposed that differing postreceptor processes couple receptor occupation to smooth muscle contraction in afferent and efferent arterioles, and that a selective inhibition of receptor-mediated afferent vasoconstriction may underlie the renal hemodynamic response to dihydropyridines.

Animals↗
PubMed1986

The role of superficial SR in modulating force development induced by Ca entry into arterial smooth muscle.

Evidence is presented for the hypothesis that the superficial sarcoplasmic reticulum (SR) of arterial smooth muscle functions as a "regulated buffer barrier" to Ca entry into the bulk of the myoplasm. Depletion of the intracellular Ca pool, which is sensitive to both norepinephrine (NE) and caffeine, decreases subsequent contraction due to high K+ depolarization. This effect is due to enhanced Ca accumulation by the SR, since it is not accompanied by a decrease in 45Ca influx. Using the Ca entry blockers D600 and La3+ to reduce tension and Ca influx during activation by NE and high K+ depolarization, we observed a threshold type of tension dependence on Ca influx. During the tonic contractile phases, the Ca influx threshold for NE-induced tension was much lower than that for high K+-increased tension. 10(-7) M NE, which discharged the SR by only 15%, caused a much smaller decrease in the Ca influx threshold for contraction, indicating that the degree of SR discharge is related to the depression of the threshold. Inositol-trisphosphate was shown to be capable of rapidly discharging Ca2+ from the SR in skinned arterial smooth muscle cells.

Animals↗