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T Maack

Publications and source records attributed to T Maack.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of atrial natriuretic factor on blood pressure and the renin-angiotensin-aldosterone system.

Atrial natriuretic factor (ANF) antagonizes vasoconstriction induced by numerous smooth muscle agonists and also lowers blood pressure in intact animals. ANF has particularly marked relaxant effects on angiotensin II-contracted vessels in vitro. Sensitivity to the blood pressure-lowering effect of ANF in vivo appears to be enhanced in renin-dependent models of renovascular hypertension compared with other experimental hypertensive models. The depressor action of low, possibly physiological doses of ANF in two-kidney, one-clip Goldblatt rats is due to a decrease in total peripheral resistance. On the other hand, high doses of ANF can lower cardiac output, particularly in volume-expanded models such as deoxycorticosterone-salt hypertension. ANF markedly inhibits renin secretion in intact animals, probably via increased glomerular filtration rate and load of sodium chloride to the macula densa. This effect is masked when renal perfusion is impaired (e.g., via unilateral renal artery constriction), in which case ANF may stimulate renin secretion slightly. ANF also reduces plasma aldosterone in vivo and inhibits basal and agonist-induced aldosterone release from isolated adrenal cortical cells. This effect appears to be especially marked for angiotensin-induced aldosterone production in vivo and in vitro. These findings indicate that ANF has potentially important interactions with the renin-angiotensin-aldosterone system and suggest a role for ANF in the homeostatic control of blood pressure as well as of extracellular fluid volume.

Adrenal Glands↗
PubMed1986

Renal hemodynamic and natriuretic effects of atrial natriuretic factor.

In this article we review the renal hemodynamic and excretory actions of atrial natriuretic factor (ANF) and consider some of the mechanisms of its vascular and natriuretic effects. ANF leads to a marked, sustained, and parallel increase in whole-organ and superficial single-nephron glomerular filtration rate (GFR) while mean blood pressure is decreased and renal blood flow (RBF) is unchanged or even decreased. The increase in GFR is caused by an efferent arteriolar vasoconstriction or by a combination of afferent vasodilation and efferent vasoconstriction. ANF also leads to a decrease in the hypertonicity of the innermedullary interstitium. Together with the increase in GFR, this phenomenon accounts wholly or in great part for the ANF-induced natriuresis. The overall renal vascular effects of ANF are complex and may tentatively be conceptualized as a behavior of a functional partial agonist: slight vasoconstriction in vasodilated kidneys, no sustained effects on the vascular resistance in normal kidneys, and vasodilation in vasoconstricted kidneys. The vasoconstrictor effect of ANF may be direct or indirect and depends on extracellular calcium whereas the antagonist effect likely results from alterations in intracellular calcium homeostasis. The data raise the perspective that ANF is not only a powerful natriuretic substance but has the potential of being an important modulator of GFR and RBF in intact animals.

Aldosterone↗
PubMed1986

Mechanism of tubular uptake on human growth hormone in perfused rat kidneys.

The mechanism of tubular uptake of labeled human growth hormone ([125I]hGH), a low molecular weight protein (approximate 21,5000 daltons), was studied in isolated perfused rat kidneys. Fractional reabsorption (FR) of [125I]hGH was decreased from 94 to 77% over a period of 80 min as perfusate oncotic pressure was lowered by reducing the albumin concentration from 7.5 to 2.5 g/100ml, whereas greater reductions in fractional sodium (delta 35%) and fluid reabsorption (delta 42%) occurred, indicating that tubular [125I]hGH uptake is likely a specific process not directly dependent upon net fluid and sodium reabsorption. Absolute absorption rates of [125I]hGH filtered loads were inhibited by cytochalasin B, a microfilament disrupter when kidneys were perfused with either albumin concentration. Cytochalasin B inhibited [125I]hGH absorption in both a dose-and time-related manner. The low dose of cytochalasin B (2.5 micrograms/ml) decreased [125I]hGH absorption without significantly altering sodium, fluid or glucose reabsorption. With high doses (5 and 10 micrograms/ml), cytochalasin B affected tubular absorption of [125I]hGH to an extent much greater than sodium, fluid and glucose reabsorption. Inhibition of cytochalasin B on FR[125I]hGH was poorly correlated with the concurrent inhibition of FRNa and FRH2O. Accordingly, tubular reabsorption of [125I]hGH is not directly linked to that of sodium, fluid and glucose. The present studies are consistent with the hypothesis that renal absorption of low molecular-weight proteins is via an endocytotic process involving microfilaments.

Absorption↗
PubMed1985

Endocytic uptake, transport, and catabolism of proteins by epithelial cells.

Adsorptive and/or receptor-mediated endocytosis of proteins is a universal cell property, which is highly expressed in epithelial cells. Some absorbed proteins are transported intact across cells and in this manner subserve specialized functions such as the transference of immunity from mother to child. Mainly, however, absorbed proteins are transported to lysosomes, where they undergo complete hydrolysis to amino acids. This process is essential for the homeostasis of circulating proteins. This brief review considers the intracellular pathways taken by endocytosed proteins and the quantitative aspects and determinants of protein uptake and catabolism by epithelial cells. The topics to be briefly discussed are initial internalization sites, transport organelles (endosomes), and lysosomal and nonlysosomal pathways of transport; intracellular sorting of internalized proteins, membranes, and receptors; kinetics and selectivity of renal cell uptake of low-molecular-weight proteins and proteohormones; receptor-mediated endocytosis of larger proteins (e.g., glycoproteins) by hepatocytes; and lysosomal catabolism of absorbed proteins and its dependence on protein load and endosomal-lysosomal pH and function. The perspectives of the field and some of the outstanding unsolved problems are briefly discussed.

Adsorption↗
PubMed1985

Effect of atrial natriuretic factor on renin secretion, plasma renin and aldosterone in dogs with acute unilateral renal artery constriction.

Atrial natriuretic factor (ANF) decreases renin secretion rate (RSR), plasma renin activity (PRA) and plasma aldosterone (PA) in normal dogs. To clarify further the mechanisms responsible for these effects, the left renal artery was constricted in seven anaesthetized dogs prior to ANF administration. Constriction of the left renal artery decreased (P < 0.05) ipsilateral mean renal perfusion pressure (MRPP, 29 +/- 7%), renal plasma flow (RPF, 42 +/- 11%) and glomerular filtration rate (GFR) and filtered sodium load (FLNa, 21 +/- 8.8%). Ipsilateral RSR and peripheral PRA tended to increase, although not significantly. Atrial natriuretic factor infusion did not alter GFR in the clamped kidney and failed to decrease RSR or PRA. Despite this, PA levels decreased significantly (7.8 +/- 2.4 to 5.6 +/- 1.8 ng%). These results suggest that ANF-induced inhibition of renin secretion is largely consequent on its renal haemodynamic actions and that suppression of aldosterone by ANF in vivo is due, in part, to direct effects on the adrenal cortex.

Aldosterone↗
PubMed1985

Atrial natriuretic factor (auriculin): structure and biological effects.

Atrial natriuretic factor (ANF) is a recently discovered peptide present in secretory granules specifically found in atrial muscle cells. Multiple structurally related peptides have been isolated from atrial tissues, all of which are derived from a common 152-amino-acid precursor. ANF induces profound natriuresis and diuresis in experimental animals and also causes relaxation of precontracted vascular smooth muscle. ANF has striking renal hemodynamic actions (most consistently an increased glomerular filtration rate), which probably explain its natriuretic effects. ANF also can inhibit renin secretion in vivo and causes direct inhibition of basal and stimulated aldosterone production. It lowers arterial blood pressure, probably reflecting in part its vasorelaxant actions, and this effect is particularly marked in renin-dependent (and possibly other vasoconstricted) models of hypertension. Although the exact structure and regulation of the presumed circulating form(s) of ANF remain to be clarified, available information suggests that it may be a new, previously unrecognized factor in the regulation of fluid volume and renal and cardiovascular function.

Aldosterone↗
PubMed1984

Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs.

Auriculin is a potent vasoactive and natriuretic peptide that was recently isolated and purified from rat atrial tissue. Since this peptide could be of great importance for renal, cardiovascular, and volume homeostasis, its functional properties have been characterized in dogs. The effects of synthetic auriculin on renal function, mean blood pressure, plasma renin activity, renin secretory rate, and plasma aldosterone levels were determined. Auriculin was administered intravenously as a prime (1.0 microgram/kg body weight) and constant infusion (0.1 microgram per minute/kg body weight for one hour) to five anesthetized dogs. In addition, two conscious dogs were used to verify some of the results obtained in anesthetized dogs. Auriculin decreased mean blood pressure from 134 +/- 5 to 122 +/- 4 mm Hg (p less than 0.05, paired t test) and increased glomerular filtration rate (25.5 +/- 2.7 to 32.4 +/- 4.1 ml per minute per kidney, p less than 0.05), diuresis (0.21 +/- 0.03 to 1.06 +/- 0.14 ml per minute per kidney, p less than 0.05), natriuresis (38 +/- 0.6 to 187 +/- 35 mueq per minute per kidney, p less than 0.05), and kaliuresis (14.8 +/- 1.6 to 35.7 +/- 6.3 mueq per minute per kidney, p less than 0.05). These effects were sustained throughout the infusion of auriculin and were entirely reversible. Renal plasma flow increased transiently for one to two minutes, and then returned to or below control levels. Urine osmolality decreased by 40 percent (p less than 0.05) whereas free water clearance remained unchanged (p less than 0.05). Auriculin reversibly decreased plasma renin activity (11.6 +/- 2.3 to 3.6 +/- 1.2 ng/ml per hour, p less than 0.05), renin secretory rate (895 +/- 313 to 255 +/- 28 ng per hour per minute, p less than 0.05), and plasma aldosterone levels (8.4 +/- 1.6 to 3.6 +/- 0.7 ng/dl, p less than 0.05), whereas plasma cortisol levels remained unchanged. These results demonstrate that auriculin has a unique combination of functional properties, increasing glomerular filtration rate, diuresis, and natriuresis, without a sustained increase in total renal blood flow, and lowering blood pressure, plasma renin levels, renin secretory rate, and plasma aldosterone levels. These properties suggest an important potential role for atrial natriuretic peptides in the regulation of renal function, extracellular volume, and blood pressure.

Aldosterone↗
PubMed1984

Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney.

The effects of rat atrial tissue extract on renal hemodynamics and fluid and electrolyte excretion were investigated in the isolated perfused rat kidney (IK). IK were perfused at a constant effective perfusion pressure of about 90 mmHg. After control clearance periods (C), extracts of rat atria (AE) or ventricles (VE) were added to the perfusate and three 10-min experimental periods followed. AE, but not VE, significantly increased (P less than 0.001) renal vascular resistance (RVR) to 133 +/- 8% of C, GFR to 201 +/- 34%, filtration fraction to 245 +/- 41%, urine flow (V) to 675 +/- 131%, fractional excretion (FE) of H2O to 336 +/- 29%, absolute Na excretion (UNaV) to 1,259 +/- 290%, FENa to 642 +/- 129%, UKV to 2,226 +/- 1,237%, and FEK to 542 +/- 119%. Despite the marked natriuresis, since GFR doubled, Na reabsorption rose from 78.3 +/- 36.3 in C to 132 +/- 36.3 mueq/min after AE. The effects of AE were immediate and lasted to the end of the perfusion. The lower the initial control GFR, the larger was the AE-induced increase in GFR. Perfusion with low [Ca] (0.2 mM) or verapamil (10(-5) M) severely blunted the hemodynamic, diuretic, kaliuretic, and natriuretic effects of AE. AE decreased rather than increased the RVR when IK were perfused with vasoconstrictors such as angiotensin II, norepinephrine, or vasopressin. The results demonstrate that AE acts directly on the kidney, eliciting powerful Ca-dependent hemodynamic and natriuretic responses. The natriuresis induced by AE can be accounted for, at least in part, by its renal hemodynamic effects rather than by the presence of a putative tubular natriuretic factor. The hypothesis is advanced that AE contains a substance(s) which behaves as a functional agonist/antagonist of endogenous vasoconstrictors with a preferential site of action on the efferent arterioles of the renal vasculature.

Animals↗
PubMed1984

Renal hydrolysis of absorbed protein: influence of load and lysosomal pH.

The kinetics of intracellular hydrolysis of administered protein and the effect of alkalinization of lysosomal pH on this process were studied in the isolated perfused rat kidney (IPK). Cytochrome c (CYT c) was used as a probe protein, and its hydrolysis was determined by measuring the efflux of radioactivity from IPK preloaded in vivo with [14CH3]CYT c and various doses of unlabeled CYT c. The nature of radioactivity absorbed by the kidney and released to the perfusate was analyzed by Sephadex chromatography. Administered CYT c is absorbed and hydrolyzed by the kidney, and the resulting amino acids are returned to the perfusate. At low uptake rates, the half time of hydrolysis of absorbed CYT c is about 20 min. The disposal of absorbed CYT c is a saturable function of its concentration in kidney with a Vmax = 0.60 mg CYT c X h-1 X g kidney-1 and an apparent Km = 0.55 mg CYT c/g kidney. To alkalinize the lysosomal pH, IPK were perfused in the presence of NH4Cl (10 mM) or chloroquine (0.1 mM). These lysosomotropic weak bases almost completely inhibit in a reversible manner the hydrolysis of absorbed CYT c. The results demonstrate that renal catabolism of absorbed protein is a saturable process of high capacity compared with the normal filtered loads of protein. The data are consistent with the view that normal lysosomal function is required for an adequate disposal of absorbed proteins in the kidney. It is postulated that abnormal deposition of protein absorption droplets within renal tubular cells may result from high absorbed loads and/or a deficient acidification of lysosomes.

Absorption↗
PubMed1984

Albumin absorption and catabolism by isolated perfused proximal convoluted tubules of the rabbit.

Overall characteristics and kinetics of tubular absorption of albumin (Alb) were studied in isolated perfused proximal convoluted tubules of the rabbit. The fate of absorbed Alb was determined in tubules perfused with low [Alb]. Alb was labeled with tritium by reductive methylation ( [3H3C]Alb). At [Alb] = 0.03 mg/ml, approximately 80% of the absorbed [3H3C]Alb was released to the peritubular bathing solution as catabolic products. Transcellular transport of intact [3H3C]Alb was negligible. Iodoacetate (IAA, 4 mM) inhibited albumin absorption (JAlb) by greater than 95% and fluid reabsorption (JV) by 55%. At [Alb] = 0.1 mg/ml the absorption rate of a derivatized cationic Alb (pI = 8.4) was fivefold greater (P less than 0.01) than that of anionic Alb. Higher cationic [Alb] had deleterious effects on tubular functions. Overall Alb absorption was of high capacity and low affinity (JmaxAlb = 3.7 ng/min per mm tubule length, apparent Michaelis constant (Km) = 1.2 mg/ml). A low capacity system that saturates at near physiological loads was also detected (JmaxAlb = 0.064 ng/min per mm, apparent Km = 0.031 mg/ml). High [Alb] did not alter the rate of endocytic vesicle formation as determined by the tubular uptake of [14C]inulin. Results show that Alb absorption is a saturable process that is inhibited by high IAA concentrations and is affected by the charge of the protein. Absorbed Alb is hydrolyzed by tubular cells and catabolic products are readily released to the peritubular side. The dual kinetics of Alb absorption may be due to a combination of adsorptive endocytosis (low capacity system) and fluid endocytosis of albumin aggregates (high capacity system). Results indicate that albuminuria occurs much before albumin absorption is saturated. The kinetic characteristics of the process of tubular absorption of albumin helps to explain the concomitance of albuminuria, increased renal catabolic rates of albumin, and renal cell deposition of protein absorption droplets in severe glomerular proteinurias.

Absorption↗
PubMed1984

Antihypertensive and aldosterone-lowering effects of synthetic atrial natriuretic factor in renin-dependent renovascular hypertension.

A 24-amino acid residue synthetic atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and aldosterone production in isolated blood vessels and adrenal cells, respectively. To determine the significance of these effects in vivo, the blood pressure and aldosterone responses to synthetic ANF were evaluated in rats with two-kidney, one clip hypertension (n = 5) and in sham-operated controls (n = 4). In the latter, ANF caused a slight fall in mean blood pressure (-7 +/- 3%) and inconsistent changes in plasma renin and aldosterone. In hypertensive rats, ANF decreased blood pressure by 31 +/- 7 mmHg (17 +/- 3%), comparable to the effect of the angiotensin antagonist saralasin (31 +/- 4 mmHg). Plasma renin activity increased from 48 +/- 15 to 79 +/- 23 ng/ml/h. Despite this, ANF caused marked suppression of plasma aldosterone (from 97 +/- 28 to 20 +/- 8.9 ng/100 ml). These results show that ANF can exert potent antihypertensive and aldosterone-lowering effects in vivo, at least when the renin-angiotensin system is stimulated.

Aldosterone↗
PubMed1982

Kinetics, competition, and selectivity of tubular absorption of proteins.

Tubular absorption (T) of two cationic proteins, lysozyme (LZM) and cytochrome c (CYT c), and two anionic proteins, beta 2-microglobulin (beta 2M) and 125I-labeled human growth hormone (hGH), was studied in the isolated perfused rat kidney. All four proteins are extensively filtered and, at low loads, almost completely absorbed by the tubular epithelium. TLZM and TCYT c is a saturable process of high capacity (Tm) and low apparent affinity. (Tm)LZM was two orders of magnitude larger than (Tm)CYT c. LZM inhibited TCYT c in a dose-dependent and reversible manner. Saturating loads of CYT c failed to inhibit T beta 2M and ThGH. Saturation, selectivity, and competition is explained on the basis of a model that incorporates adsorption of protein to microvilli as well as geometric and electrical constraints on the access of filtered proteins to endocytic sites at the base of the microvilli. Tubular absorption of all proteins is decreased by inhibitors of the formation and/or internalization of endocytic vesicles (iodoacetate and cytochalasin B). However, lysine (5 mM) and low perfusate calcium concentration (0.5 mM) inhibited T beta 2M but not TCYT c and ThGH. The selective effect of 5 mM lysine, which causes morphologic damage in initial portions of the proximal convoluted tubule, may be due to preferential or exclusive absorption of beta 2 M in this portion of the nephron. The results as a whole demonstrate that in addition to net charge other structural features of the protein molecule and of the luminal wall of proximal tubules may be important determinants of the efficiency and capacity of the tubular absorption of filtered proteins.

Animals↗
PubMed1981

Sodium-calcium interactions in the renal proximal convoluted tubule of the rabbit.

The effect of experimental maneuvers believed to raise cytosolic [Ca2+] on Na and fluid absorption by isolated perfused proximal convoluted tubules of rabbit kidneys was examined. For this purpose experiments were carried out in which either 1) peritubular [Na] was lowered from 145 mM in controls to 40 mM in experimental periods by isosmotic replacement with Li, tetraethylammonium, or choline; or 2) quinidine (10(-4) M) or A 23187 (5 X 10(-6) M) was added to the peritubular bath containing 145 mM Na. Fluid absorption (Jv), transepithelial unidirectional Na efflux (JNa 1 leads to b), and Na influx (JNa b leads to 1) were measured. Lowering peritubular [Na] inhibited JNa 1 leads to b by 28% and Jv by 61% of the control values. The degree of inhibition of Jv by low peritubular [Na] was dependent on the concentration of ultrafilterable calcium ([Ca]UF) over the range of 0.2-1.0 mM: as perfusate and bath ultrafilterable calcium was reduced, there was an attenuation of the low [Na]-induced inhibition of Jv. Above 1.0 mM [Ca]UF no further increase in inhibition of Jv was observed. Quinidine in the bath inhibited Jv by 37% and JNa 1 leads to b by 28%; A 23187 reduced Jv by 37% and JNa 1 leads to b by 15%. These results are consistent with the view that cytosolic [Ca2+], in turn dependent on a Na-Ca exchange mechanism located at the basolateral cell membrane, regulates, in part, the rate of proximal tubular efflux of sodium, calcium, and water.

Animals↗
PubMed1980

Physiological evaluation of the isolated perfused rat kidney.

A critical evaluation of the functional properties of the isolated perfused rat kidney is necessary to assess the usefulness of the preparation for renal function studies. Clearance and micropuncture experiments in isolated perfused rat kidneys perfused with a plasmalike medium containing 7.5 g/100 ml albumin, glucose, and amino acids show that proximal convoluted tubule functions are well preserved. Proximal convoluted tubule reabsorption of organic substances, electrolytes, and fluid is near normal, the latter being directly related to the peritubular oncotic pressure. Superficial single nephron glomular filtration rate and glomerular permselectivity are also preserved. However, abnormalities in renal hemodynamics, urinary concentration-dilution, and excretion of fluid and electrolytes persist even in the best preparations. High renal perfusate flow, due mainly to the low viscosity of the perfusate, and altered distal nephron functions explain at least in part these abnormalities. Therefore, the isolated perfused rat kidney is a useful preparation to particularly study glomerular and proximal convoluted tubule functions. Recent development of a nonfiltering isolated perfused rat kidney model, with preserved renal perfusate flow and cellular integrity, also permits the study of transport and metabolic functions of proximal tubular cells independently of luminal events.

Animals↗