PubMed Health⌕ Search

Biomedical subjects

V Horácek

Publications and source records attributed to V Horácek.

At least 19 recordsLinked to original sources
PubMed2000

Effect of intrarenal infusion of angiotensin-(1-7) in the dog.

Angiotensin-(1-7), (Ang-(1-7)), a metabolite of Ang II and /or Ang I, was infused into the renal artery (i.r.a) of anesthetized dogs in order to demonstrate its possible direct renal action. The dose administered, 15 Ig/kg BW/min in isotonic saline (0.072 ml/kg BW/min) throughout the experiment, did not influence the systemic arterial pressure and water and sodium excretion from the contralateral noninfused kidney. Renal blood flow (RBF) was measured by an electromagnetic flowmeter, glomerular filtration rate (GFR) by (exogenous) creatinine clearance. In other groups of animals, either EXP 3174, an AT-1 receptor antagonist alone (30 Ig/kg BW/ min) or together with Ang-(1-7) (15 Ig/kg BW/min), were infused. In the last group, the AT-2 receptor antagonist PD 123319, 10 Ig/kg BW/min, was added to the infusion of Ang-(1-7). A small but significant decrease of RBF from 4.51+/-0.32 to 3.8+/-0.29 ml/g BW/min occurred after Ang-(1-7); this decrease was very similar when PD 123319 was added. However, an increase to 4.98+/-0.34 ml/g BW/min was seen after the addition of EXP 3174 to the i.r.a. infusion of Ang-(1-7); this increase was similar to the increase observed after EXP 3174 alone (5.21+/-0.33; p<0.02 in both cases). A very small but significant increase in GFR was seen after Ang-(1-7) + EXP 3174 or after the AT-1 blocker alone (0.64+/-0.049 and 0.62+/-0.05 vs. 0.6+/-0.05 ml/g BW/min in the Time Control Group, p<0.01 and 0.05, respectively). Water, sodium and urea excretion rates were increased in all groups infused with Ang-(1-7); after the combination of Ang-(1-7) + EXP 3174, all increases were higher than after every substance alone; however, statistical significance (p<0.05) was reached in sodium excretion values only. Potassium excretion rates were increased just in those groups in which EXP 3174 was present in the infusion fluid. In summary, Ang-(1-7) i.r.a. infusion in the dog is followed by increases in water, sodium and urea (but not potassium) excretion rates, highly probably of tubular origin. This effect is not completely blocked by the AT-1 - and not at all by the AT-2 receptor antagonist - thus indirectly suggesting another receptor could play a role. A small decrease in RBF disappears after EXP 3174, thus indicating an AT-1 receptor action.

Angiotensin I↗
PubMed1997

Glomerular haemodynamics during renal artery clamping and haemorrhage in the dog.

The influence of gradual decline in renal perfusion pressure (RPP) due either to renal artery clamping (C) or to haemorrhagic hypotension (HH) was studied using micropuncture techniques in anaesthetized dogs. The decrease in renal blood flow (RBF) was more profound and set in earlier during HH than during C, where perfect autoregulation was observed down to a mean arterial blood pressure of 85 mmHg. Glomerular filtration rate (GFR) was also only slightly decreased during C, with no change in filtration fraction (FF); again, a much greater decrease in GFR with an increase in FF was seen in HH. The excretion of water, electrolytes and urea were also more decreased during HH than during C. Similar changes were seen at the single nephron (SN) level. Opposite changes were observed in arteriolar resistances: during C a decrease in total arteriolar resistance (RT) amounting to -22% at a RPP of 84 mmHg and -13% at 60 mmHg was seen, due exclusively to a drop in afferent resistance (RA), but during HH there was a significant increase in RT by +36% at RPP of 110 mmHg, +39% at 85 mmHg and +68% at 60 mmHg. This increase was mainly due to an increase in efferent resistance (RE) rather than in RA: +42 vs. +31%, respectively, at 110 mmHg and +67 vs +19% respectively, at 85 mmHg. It was not until a RPP of 60 mmHg was reached that this difference between RE and RA disappeared, being +67% for RE and +69% for RA. The ultrafiltration coefficient, Kf, did not change during C and only decreased slightly with the biggest drop in RPP during HH (2.84 microliters mmHg-1 min-1 during HH vs. 4.19 microliters mmHg-1 min-1 before HH). The SNGFR/GFR ratio remained unchanged during C but declined with decreasing RPP during HH, which probably indicates a 'redistribution' of RBF to the deeper regions of the renal cortex. In conclusion, major differences in renal function were observed between C and HH whose cause is unknown.

Animals↗
PubMed1997

Effect of PD 123319, an AT-2 antagonist, on renal function of the anesthetized dog: comparison with EXP 3174, an AT-1 blocker.

In anaesthetized dogs fed a diet delivering 3.5 mmol NaCl/kg/day, PD 123319 - an angiotensin (AT) II (Ang II) antagonist preferentially bound to AT-2 receptors - was infused into the renal artery for 20 min at 10 microg/kg/min, the lowest effective dose (group 1 dogs). In group 2 dogs, EXP 3174 (30 microg/kg/min) - an AT-1 blocker - was coinfused while, in group 3, EXP 3174 was infused alone. In all groups, during and immediately after infusion, increased sodium, water, and urea excretions from the infused but not from the contralateral kidney were seen. This increase was the same in all groups throughout the infusion; however, in groups infused with EXP 3174, it persisted even after the infusion had been discontinued. Thus, the total amounts of sodium and water excreted during the whole experiment were higher when EXP 3174 was present in the infusion solution than after PD 123319 alone. Moreover, an increase in glomerular filtration rate (creatinine clearance) and renal blood flow (electromagnetic flowmeter) was seen during the infusion period in groups receiving EXP 3174, but not PD 123319. Although it is possible to assume that blockade of AT-1 receptors only is responsible for the changes in excretion rates as PD 123319 is known to interact with these receptors at high concentrations, it is difficult to explain why it does not react with the same receptors responsible for changes in glomerular filtration rate and renal blood flow. An alternative explanation assumes that the excretory changes are due to blockade of both AT-1 and AT-2 receptors; the identity in effect and the absence of additivity of both antagonists could be explained by the existence of a final common pathway leading to the inhibition of the Ang II effect. This pathway could be reached either from AT-1 or AT-2 receptors.

Angiotensin Receptor Antagonists↗
PubMed1997

Comparative effects of the angiotensin II receptor blocker EXP 3174 and of the angiotensin-converting enzyme inhibitor captopril on renal glomerular hemodynamics in the dog.

The effects on glomerular hemodynamics of angiotensin-converting enzyme (ACE) inhibition with captopril and of angiotensin II receptor blockade with EXP 3174, an active metabolite of losartan, either alone or in combination, were compared in anesthetized dogs. Administration of EXP 3174 intrarenally led to an increase in renal blood flow by +14% and in glomerular filtration rate by +7%, thus decreasing the filtration fraction by -5%. Similar changes were observed at the single-nephron level. Water, sodium, potassium, and urea excretion rates rose considerably. A decrease in effective filtration pressure by -27% and an increase in ultrafiltration coefficient, Kf, by +57% were seen. A drop in total arteriolar resistance by -19% was mainly due to a decrease in efferent (-25%) rather than afferent (-14%) resistance. When captopril, an ACE inhibitor, was administered intravenously after and during EXP 3174, an additional increase in renal blood flow, by +8%, with no change in glomerular filtration rate was seen which led to an additional decrease in filtration fraction by -5%; additional increases were observed in water and urea but not in sodium and potassium excretion rates. An additional decrease in total arteriolar resistance, by -14%, was now evenly distributed between the efferent (-6%) and afferent (-8%) arterioles. Almost all of these additional changes disappeared when a bradykinin B2-antagonist, Hoe 140, was infused together with captopril. In conclusion, administration of an ACE inhibitor led to a significantly enhanced vasodilatory response in the kidney as compared with the administration of an angiotensin II-receptor blocker. This enhancement was almost eliminated by the coadministration of Hoe 140, thus rendering the participation of kinins fairly plausible.

Adrenergic beta-Antagonists↗
PubMed1994

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog.

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i.v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 micrograms kg-1 min-1. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B2 receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min-1 g kidney weight-1 and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min-1 g-1. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, Kf, by 103% from 3.55 nl/mmHg to 7.19 nl/mmHg (26.7-54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

The cause of a depressed glomerular filtration rate after an ischaemic insult: whole kidney and superficial nephron study in the dog.

Twenty-four hours after 90 min clamping of the left renal artery in dogs, the glomerular filtration rate (GFR) was decreased in the whole kidney (0.34 ml.min-1g KW-1 [KW = Kidney weight] vs 0.64 in contralateral unclamped kidney) just as in the single nephron (SNGFR, 19.7 vs 51.8 nl.min-1). Renal blood flow (RBF) did not change; single nephron glomerular blood flow (SNGBF) was decreased by 9% only. After injection of Lissamine green into the renal artery, brief diffuse tinting of the whole kidney surface was observed. Thereafter, patchy coloration - corresponding to passage of the dye through patient tubuli - took place in approximately one-quarter to one-third of the kidney surface. Micropuncture measurements were carried out in these areas. The values of hydraulic pressure in peritubular capillaries and proximal convolutions were not different from those found in controls; directly measured glomerular capillary pressure was decreased (48.7 vs 59.5 mmHg). The ultrafiltration coefficient(Kf) was significantly depressed (2.7 vs 3.8 mmHg.nl-1.min). Total kidney and arteriolar resistances remained unchanged but afferent resistance (RA) was elevated (11%) and efferent resistance (RE) was lowered (23%) compared with those of controls. Ninety-seven percent of proximally microinjected 3H-inulin was recovered from the control kidney but only 85% from the kidney rendered ischaemic. In conclusion, the typical findings at 24 h after 90 min ischaemia are low GFR and SNGFR with normal RBF and almost normal superficial SNGBF values. This phenomenon is mainly due to a decrease in Kf and a decrease in RE with a simultaneous increase in RA; back-leak through damaged tubuli seems to play only a minor role.

Animals↗
PubMed1990

The effect of two different calcium antagonists on the glomerular haemodynamics in the dog.

Kidney function of beagles fed a constant amount of food containing 3 mmol sodium.kgbodywt-1.day-1, and anaesthetized with pentobarbitone was investigated by clearance and micropuncture techniques during an intrarenal infusion of saline or the calcium antagonists verapamil (VER, 4 micrograms.kgbodywt-1.min-1) or nifedipine (NIF, 0.3 microgram.kgbodywt-1.min-1). Neither drug changed the mean arterial pressure. Apart from the natriuresis and diuresis, which were significantly greater with NIF than with VER, the response to both drugs was similar. Increases in renal blood flow (RBF; 17% with VER, 20% with NIF), glomerular filtration rate (GFR; VER: 34%; NIF: 39%) and filtration fraction (VER: 12%; NIF: 14%) were observed; similar values were obtained at the single nephron level. Pressure in glomerular capillaries, measured directly after ablation of a thin layer of cortex corticis, was increased by 11% with VER and 10% with NIF; no changes in proximal tubular and peritubular capillary pressure were seen. The glomerular ultrafiltration coefficient (Kf) did not change with either drug. Total arteriolar resistance was decreased (VER: 20%; NIF: 15%) due to a decrease in afferent resistance (VER: 31%; NIF: 27%) with no corresponding change in efferent resistance. The cause of the lack of responsiveness of the efferent arteriole remains unclear. In conclusion, in acute experiments with intrarenal administration, both drugs increase RBF and GFR by a preferential afferent dilatory mechanism without any change in Kf.

Animals↗
PubMed1988

A possible role for leukotrienes in the regulation of glomerular haemodynamics in the dog.

In anaesthetized beagles, saralasin, phentolamine, 1-penicillamine-2-O-methyl-tyrosine-8-arginine-vasopressin and SCH 23390, a DA1 antagonist, were infused into the left renal artery (i.r.a.) and indomethacin and aprotinin intravenously (Group 1). In Groups 2 and 3, i.r.a. infusion of two chemically different putative leukotriene (LT) antagonists, FPL 55712 (100 micrograms/kg/min) and LY 171883 (500 micrograms/kg/min), respectively, was superimposed in the fourth period of experiments. In comparison to Group 1, there was an increase (40% in Group 2 and 33% in Group 3) in renal blood flow and a decrease in glomerular filtration rate (16% and 17%, respectively) and filtration fraction (36% and 41%, respectively). Similar changes were observed on the single nephron level. Directly measured glomerular capillary pressure decreased by 10% and 12%, respectively. A decrease in total arteriolar resistance by 34% and 25%, respectively, was caused by a comparatively higher decrease in efferent (44% and 34%, respectively) than afferent (26% and 15%, respectively) arteriolar resistance values. No change in the ultrafiltration coefficient, Kf, was detected. Providing FPL 55712 and LY 171883 are specific LT antagonists, these experiments suggest a possible constrictory role of LT (expressed more on the efferent than afferent arteriole) in anaesthetised mildly surgically stressed dogs.

Acetophenones↗
PubMed1987

Protein aggregates in extracorporally perfused rabbit kidneys.

Eighteen rabbit kidneys were perfused ex vivo for 1 h with allogeneic blood, and in 16 a solution of xenogeneic aggregate-free, aggregated or antibody-complexed protein was added to the perfusate 5 min after the start (human immunoglobulins or serum albumin, partly cationized, were used). The kidneys were examined by light and electron microscopy and the human and rabbit immunoglobulin (or albumin) precipitates were detected by direct immunofluorescence and ultrastructural immunohistochemistry. In 13 kidneys the perfusion produced small segmental glomerular endocapillary aggregates of platelets, leukocytes, and granular precipitates reactive with both anti-rabbit and anti-human antibodies. No typical deposits were seen in mesangium or in periphery of glomerular capillaries but rabbit Ig penetrated to the inter- and subepithelial spaces of proximal convoluted tubules. Three kidneys perfused by cationized aggregated human Ig (or by cationized albumin-antialbumin complexes) exhibited a destructive lesion with rapid breakdown of blood flow and massive global endocapillary plugs of similar ultrastructure but with focal endothelial sloughing. Pericapillary granular precipitates of human and rabbit Ig were seen in these kidneys. When the blood with cationized Ig aggregates was used for perfusion of two further kidneys extensive endocapillary aggregates with endothelial damage reappeared but the extracapillary penetration and precipitation were lacking and the blood flow largely improved. Membrane polyanion of podocytes stained by colloidal iron was preserved even in close proximity of cationized complex precipitates. Thus, in the ex-vivo perfusion model the preformed neutral aggregates did not penetrate through the glomerular capillary wall and were not phagocytized by mesangial cells. The cationized aggregates induced rapid circulatory failure with massive platelet clumping and granular pericapillary "humps" ultrastructurally different from the deposits of human and experimental immune complex glomerulonephritis.

Animals↗
PubMed1987

Prostacyclin prevents hyperacute xenogenous rejection of the kidney.

The rabbit kidney, perfused under a constant pressure from the canine femoral artery is rejected (i.e. blood flow arrests) within several minutes. It cannot be prevented by intraarterial infusion of strong vasodilatators, such as verapamil and prostaglandin E2. Prostacyclin PGI2 infusion is capable of maintaining a sufficient blood flow and urine production in the rabbit kidney as long as the infusion continues. Once the infusion is interrupted, signs of hyperacute rejection immediately appear. PGI2 or its analogue with a prolonged halflife seem promisive in the treatment of the transplanted kidney rejection.

Animals↗
PubMed1987

Hemodynamics of the recently opened glomeruli. Micropuncture study in 22- to 26-day-old puppies.

In 22- to 26-day-old beagle puppies, just after superficial nephrons have begun to function, the single nephron glomerular filtration rate is extremely low (6.7 nl.min-1) approximating a tenth of the adult value (57 nl.min-1) even though blood pressure is as high as 90 mm Hg. Glomerular vascular resistance is almost six times the value found in the adult dog (1.8 vs. 0.32 mm Hg.ml-1.min), this increase being mainly due to a rise in afferent (80%) rather than in efferent (20%) resistance. The glomerulus, having only recently started to function, is characterized by filtration pressure equilibrium, a phenomenon atypical of superficial glomeruli in the adult dog. These findings favor the concept that a low glomerular blood flow rate might be the main cause of the very low SNGFR in the new glomeruli, although some contribution of an altered ultrafiltration coefficient cannot be excluded.

Animals↗
PubMed1986

Angiotensin II: preferential efferent constriction?

In dogs with maximal subpression of endogenous angiotensin II (AII) production due to a high-salt diet and converting enzyme inhibition (CEI, SQ 14,225, 15 micrograms X kg-1 X min-1 i.v.), infusion of a subpressor dose of angiotensin II (1 ng X kg-1 X min-1) did not change contralateral kidney function. In the infused kidney, a decrease in renal blood (RBF) by 24% and glomerular filtration rate (GFR) by 9% with an increase in filtration fraction (FF) by 20% occurred. Similarly, the increase in single nephron (SN) RBF was greater than in SNGFR, thus rising SNFF by 8%. Glomerular capillary pressure (GCP) did not change significantly; a decrease by 20% in proximal tubule pressure thus resulted in an increase in delta HP by 22%. This increase counterbalanced the profound drop in ultrafiltration coefficient (Kf) (57%) making the decrease in GFR and SNGFR relatively small. Total arteriolar resistance (RT) rose by 26%, the rise being due mainly to an increase in efferent (RE, 50%) rather than afferent (RA, 4%) resistance. If the AII infusion was carried out during concomitant infusion of CEI and indomethacin (1 mg X kg-1 X min-1) or aspirin (5 mg X kg-1 X min-1), RBF decreased by 36%, GFR by 25%, thus increasing FF by 18%; corresponding SN values underwent similar changes. Drop in Kf amounted to 62% and hydraulic pressure difference (delta HP) increased by 11% with unchanged GCP. The increase in RT (72%) was now due to a very similar increase in both RA (68%) and RE (76%). In conclusion, a very small dose of AII exhibits-at least in superficial nephrons-a typical preferential efferent effect which disappears after inhibition of prostanoid synthesis, indicating a protective effect of vasodilatory prostaglandins mainly on the afferent arteriole.

Angiotensin II↗
PubMed1984

Kidney function during decreased perfusion pressure due to aortic clamping and hemorrhagic hypotension: a single nephron study in dog kidney.

Whole kidney and single nephron function was compared in dogs during a stepwise lowering of renal perfusion pressure (PP) induced by aortic clamping (C) or hemorrhagic hypotension (HH). In C, renal vascular resistance (RVR) decreased with decreasing PP, the decrease being due to a drop in afferent resistance (RA) only. HH was associated with a rise in RVR due in the first phase mainly to an increase in RE, later to both RA and RE. There was a decrease in total kidney blood flow (RBF), glomerular filtration rate (GFR), glomerular and peritubular capillary pressure, and proximal tubular pressure. In C, RBF and GFR showed no significant difference at PPs 17 and 13 kPa. However, single nephron pressures were slightly but significantly lowered. In both groups, glomerular capillary hydraulic pressure (GCP) was significantly higher when calculated as SFP + piA (stop flow pressure + systemic arterial plasma oncotic pressure) than when measured directly by puncturing glomerular capillaries after ablation of a small layer of superficial cortex. This difference disappeared at PP 8 kPa. Ultrafiltration coefficient (Kf) seemed to increase with decreasing PP.

Animals↗
PubMed1980

Comparison of directly measured and calculated glomerular capillary pressure in the dog kidney at varying perfusion pressure.

To gain access to glomeruli of the dog kidney, an approximately 0.3 mm thick superficial tissue layer was cut off from the convexity of the kidney. The surface was superfused with warm Ringer's. Renal perfusion pressure (PP) was changed by an aortic clamp. The afferent oncotic pressure (pi A) was calculated from arterial plasma protein concentration, the efferent (pi E) from pi A and single nephron filtration fraction. At PP 17 and 13kPa, directly measured GCP was significantly lower than that calculated from stop-flow pressure (SFP + pi A). At PP8kPa, the difference was not significant. Hydraulic pressure differences across the glomerular capillary wall was still significantly different from pi E at PP 17 and 13 kPa. Hence, filtration pressure equilibrium was achieved in the dog kidney only at PP 8kPa.

Animals↗
PubMed1979

Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney.

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 micrometer in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent "redistribution" of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be somewhat higher than that of total RBF autoregulation.

Animals↗