PubMed Health⌕ Search

Biomedical subjects

C Judes

Publications and source records attributed to C Judes.

At least 19 recordsLinked to original sources
PubMed1997

Postnatal development of vascular resistance of the rabbit isolated perfused kidney: modulation by nitric oxide and angiotensin II.

Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.

Age Factors↗
PubMed1996

Parathyroid hormone-related protein detection and interaction with NO and cyclic AMP in the renovascular system.

The presence of parathyroid hormone-related protein (PTHrP) in human kidney vasculature and the signal transduction pathways stimulated during PTHrP-induced vasodilation of the rabbit kidney were investigated. Immunostaining of human kidney revealed the abundant presence of PTHrP in media and intima of all microvessels as well as in macula densa. In isolated perfused rabbit kidney preconstricted with noradrenaline, 10(-5) M Rp-cAMPS, a direct inhibitor of protein kinase A, produced comparable inhibition of 2.5 x 10(-7) M forskolin- and 10(-7) M PTHrP-induced vasorelaxations. Renal vasorelaxation and renal microvessel adenylyl cyclase stimulation underwent comparable desensitization following exposure to PTHrP. Nitric oxide (NO)-synthase inhibition by L-NAME (10(-4) M), NO scavenging by an imidazolineoxyl N-oxide (10(-4) M) and guanylyl cyclase inhibition by methylene blue (10(-4) M) decreased PTHrP-induced vasorelaxation by 27 to 53%, abolished bradykinin-induced vasorelaxation and did not affect forskolin-induced vasorelaxation. The effects of Rp-cAMPS and L-NAME were not additive on PTHrP-induced vasorelaxation. Damaging endothelium by treating the kidney with either anti-factor VIII-related antibody and complement, gossypol or detergent, did not affect PTHrP- or forskolin-induced vasorelaxations but reduced bradykinin-induced vasorelaxation by 53 to 92%. Conversely, endothelial damage did not alter the inhibitory action of L-NAME on PTHrP-induced vasorelaxation. In conclusion, PTHrP is present throughout the human renovascular tree and juxtaglomerular apparatus. Activation of both adenylyl cyclase/protein kinase A and NO-synthase/guanylyl cyclase pathways are directly linked to the renodilatory action of PTHrP in a way that does not require an intact endothelium in the isolated rabbit kidney.

Adenylyl Cyclases↗
PubMed1994

Involvement of nitric oxide in the vasodilatory response to parathyroid hormone-related peptide in the isolated rabbit kidney.

1. The present study was designed to explore the role of NO derived from L-arginine in the vasodilatory response to synthetic human parathyroid hormone-related peptide-(1-34) in the isolated rabbit kidney perfused in the presence of indomethacin (10 mumol/l) and preconstricted with noradrenaline (7.2 nmol/min). 2. Under control conditions, bolus administrations of acetylcholine (10 mumol/l), an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent renal vasodilator, and parathyroid hormone-related peptide (87 nmol/l) decreased the preconstriction pressure, by 31%, 71% and 43%, respectively. 3. Bolus administration of 100 mumol/l NG-nitro-L-arginine-methyl ester caused a 20% increment in the perfusion pressure of the noradrenaline-preconstricted kidney. NG-nitro-L-arginine methyl ester inhibited the vasodilatory effect of acetylcholine and parathyroid hormone-related peptide, by 68% and 44%, respectively, but did not alter the verapamil-induced vasodilatation. 4. Unlike L-arginine, the bolus administration of 1 mumol/l of a mono-substituted L-arginine derivative, N-alpha-benzoyl-L-arginine ethyl ester, durable decreased the noradrenaline/NG-nitro-L-arginine methyl ester-induced preconstriction by 57%. 5. Both L-arginine and N-alpha-benzoyl-L-arginine ethyl ester effectively reversed the inhibition induced by NG-nitro-L-arginine methyl ester on the vasodilatation elicited by acetylcholine and parathyroid hormone-related peptide. 6. In conclusion, the formation of NO from L-arginine contributes a substantial part to the vasodilatory action of parathyroid hormone-related peptide. Therefore, parathyroid hormone-related peptide appears to have a place among the renal haemodynamically active substances, whose vasodilatory actions are tuned by NO.

Acetylcholine↗
PubMed1993

Evidence for adenylyl cyclase-dependent receptors for parathyroid hormone (PTH)-related protein in rabbit kidney glomeruli.

Studies were conducted to test whether parathyroid hormone-related protein (PTHrP) is able to stimulate adenylate cyclase activity in isolated rabbit glomeruli. Maximal stimulations were reached at 10(-7) M of human PTHrP-(1-34) or rat PTH-(1-34) and showed a 3-3.3 fold increase over basal activity. The potency (EC50) values were close to 10(-9) M. The guanyl nucleotide GTP, at 10(-5) M, potentiated the effect of PTH and PTHrP but reduced their potency. The combined effect of maximal concentrations of PTHrP and PTH was not additive, and the PTH antagonist [Nle8.18, Tyr34]-bPTH-(3-34)amide inhibited both PTHrP- and PTH-stimulated adenylate cyclase activities. These findings suggest that PTHrP could affect glomerular function through changes in glomerular cAMP content by interaction with PTH receptors.

Adenylyl Cyclases↗
PubMed1993

Renin stimulating properties of parathyroid hormone-related peptide in the isolated perfused rat kidney.

Previous studies showed that PTHrP exhibits renal vasodilating, arteriolar cAMP stimulating and receptor binding properties. The present experiments were designed to study whether PTHrP may influence renin secretion. Rat kidneys were isolated and single-pass perfused at constant flow and stabilized pressure. Exposures to PTHrP or PTH stimulated a dose-dependent renin release reaching similar Vmax. The affinity (0.1 nM) and threshold concentration (0.01 nM) for PTHrP were about 10 times lower than for PTH. Compared to 10 microM isoproterenol, the maximum renin responses to PTHrP were similar but of shorter duration. The PTHrP dose-response curve was not affected by 10 microM indomethacin. Administered simultaneously, PTHrP and PTH displayed no additive effects. PTHrP-induced renin release as well as the role of extracellular calcium were further studied in nonfiltering kidneys, which were perfused at a constant flow and stable pressure in a closed circuit. Basal renin release was inversely related with perfusate calcium and was depressed by the calcium ionophore BAY-K8644. PTHrP (100 nM) induced a 1.6-fold increase of basal renin release in normocalcic perfusate. Removing calcium abolished renin responses. PTHrP reversed the inhibiting effects of hypercalcic media or BAY-K8644 on basal renin release. The results support calcium-mediated renin stimulating properties for PTHrP, via PTH receptors, independently from baroreceptors, macula densa and prostaglandins.

Animals↗
PubMed1993

Stimulatory action of parathyroid hormone on renin secretion in vitro: a study using isolated rat kidney, isolated rabbit glomeruli and superfused dispersed rat juxtaglomerular cells.

1. We have previously reported that pharmacological concentrations (125nmol/l) of parathyroid hormone may stimulate renin release in the stable recirculating and non-filtering isolated rat kidney. 2. In the present study we have attempted to extend these initial observations by examining the concentration-related response of renin release to parathyroid hormone, using the same model of isolated kidney, and determining whether the effect of parathyroid hormone on renin release can be demonstrated by more direct approaches. Thus, the effects of parathyroid hormone on renin secretion were investigated in two other renal preparations: isolated rabbit glomeruli and isolated rat juxtaglomerular cells. 3. In the isolated kidney, rat parathyroid hormone significantly stimulated renin accumulation in the perfusate in a concentration-related manner with a threshold of 1 nmol/l. 4. In both glomeruli and juxtaglomerular cells bovine [Nle8,18,Tyr34]parathyroid hormone-(1-34)amide effectively and repeatedly stimulated renin release. These results imply that there is a direct stimulatory effect of parathyroid hormone on renin release. 5. We also examined the effect of [Nle8,18,Tyr34]parathyroid hormone-(1-34)amide during extracellular calcium buffering in the glomeruli. [Nle8,18,Tyr34]parathyroid hormone-(1-34)amide was uneffective in calcium-free medium. Increasing the extracellular ionized calcium concentration to 2.5 mmol/l increased the extent of stimulation in accordance with the reported ability of parathyroid hormone to block calcium channels and relax vascular smooth muscle cells. 6. These results provide further support for the role of parathyroid hormone as a direct mediator of renin secretion; moreover, the renin-stimulating action of parathyroid hormone may be mediated through the inhibition of calcium influx.

Animals↗
PubMed1991

Parathyroid hormone and calcium: interactions in the control of renin secretion in the isolated, nonfiltering rat kidney.

The present study was designed to characterize the interaction of calcium and PTH in the control of renin release in isolated rat kidneys perfused in a closed circuit at constant flow. Kidneys were rendered nonfiltering using low perfusion pressures (70 mm Hg) and a hyperoncotic perfusate (100 g/liter BSA). Under these conditions, differences in perfusion pressure were less than 9 mm Hg between control and PTH-treated kidneys over the 50 min of perfusion. In the absence of PTH, renin release was inversely correlated with ionized calcium (Ca2+) concentration, with the highest release of renin noted with 1 mM EGTA and no added calcium. Also, verapamil treatment markedly elevated renin release, even in the presence of 2 mM Ca2+. In contrast, renin secretion was strongly depressed by 20 nM BAY-K8644 in the perfusate. In medium containing normal calcium concentrations (1 mM Ca2+), rat PTH(1-34) induced a 2-fold greater renin accumulation than in the control, non-PTH-treated kidneys. Isoproterenol induced a 5-fold stimulation under the same conditions. In the 0 Ca2+/1 mM EGTA perfusion, PTH did not elevate renin secretion. Renin release in response to PTH in 2 mM Ca2+ was similar to that observed in the 1 mM Ca2+ perfusion. PTH also reversed the effects of BAY-K8644 to suppress renin release. In verapamil-treated kidneys, PTH failed to stimulate renin release. These results indicate that PTH stimulates renin release by a process independent of the baroreceptors and macula densa. The Ca2+ modulation of PTH-induced renin release is consistent with the reported ability of PTH to block calcium channels and relax vascular smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Renal vasodilatation and microvessel adenylate cyclase stimulation by synthetic parathyroid hormone-like protein fragments.

The hypercalcemia caused by malignancy factor, also called parathyroid hormone-related protein (PTHrP), exhibits most of the biological activities of parathyroid hormone (PTH) in kidney and bone. On the basis of the well-documented vascular action of PTH, we characterized the vasodilator action of human (h) PTHrP-(1-34) on a preparation of the isolated rat kidney, and its activity to stimulate adenylate cyclase in microvessels isolated from rabbit kidney cortex. Injection of sequential cumulative doses of hPTHrP-(1-34) into the isolated kidney preparation produced increasing vasodilatation up to 10(-8) M (EC50 of 3 x 10(-9) M) and decreasing responses thereafter. The maximal effect represented 26% of the reference relaxation induced by papaverine. Single injections of hPTHrP-(1-34) resulted in a greater (over 60%) vasodilatation. These results were reminiscent of the tachyphylaxis that occurs after repeated exposure to the peptide. The (3-34) PTH antagonist inhibited the hPTHrP-induced vasodilatation. Human PTHrP-(1-34) was equipotent with hPTH-(1-34) (EC50 values of 3 x 10(-9) M) but 5-fold less potent than rat (r) PTH-(1-34) in stimulating microvessel adenylate cyclase. GTP enhanced the enzyme responses to the peptides but reduced their potency. Both (3-34) and (7-34) PTH antagonists were inhibitors of hPTHrP- or PTH-stimulated microvascular adenylate cyclase. Synthetic hPTHrP-(1-16) had neither vasodilator nor adenylate cyclase-stimulating activity. This hPTHrP fragment exhibited some inhibitory effect on the hPTHrP-(1-34)-induced stimulation of microvessel adenylate cyclase. These results indicate that hPTHrP possesses PTH-like activity to cause vasorelaxation and to stimulate microvascular adenylate cyclase in the kidney.

Adenylyl Cyclases↗
PubMed1988

Effect of prostaglandin E2 on adenylate cyclase activity in isolated glomeruli and tubules during postnatal maturation of rat renal cortex.

To examine the effect of prostaglandins on adenylate cyclase during the postnatal maturation of kidney, the prostaglandin E2 (PGE2) responsiveness of adenylate cyclase in the absence and presence of exogenous GTP was investigated in glomeruli and tubules isolated from renal cortex of 14-, 21- and 30-day-old rats. In the absence of GTP, the adenylate cyclase response to PGE2 in glomeruli of 14-day-old rats was about fourfold higher than that in 21- and 30-day-old rats. In the tubules there was an about 30-35% decrease in the enzyme response to the prostaglandin between 14 and 21 days as well as between 21 and 30 days. When GTP was present, the PGE2 responsiveness of adenylate cyclase was of the same order of magnitude in glomeruli at 14 and 21 days and lower at 30 days. Under the same conditions, no significant changes were observed in the cortical tubules throughout the period studied. Thus association of PGE2 plus GTP suggests that during the postnatal maturation of rat kidney, the response of adenylate cyclase to PGE2 remains unchanged in cortical tubules and slightly decreases in glomeruli.

Adenylyl Cyclases↗
PubMed1987

Structure-activity relationship of parathyroid hormone: relative sensitivity of rabbit renal microvessel and tubule adenylate cyclases to oxidized PTH and PTH inhibitors.

It has been shown previously that secondary structural changes of bPTH-(1-34) (synthetic amino-terminal (1-34) fragment of bovine parathyroid hormone), obtained by oxidation of the methionines 8 and 18, abolished its hypotensive but not its hypercalcemic action. Hence, it has been postulated that the various physiological effects of the hormone are mediated by different receptors that require different regions or configurations of the peptide. To further examine this hypothesis the relative sensitivity of the PTH-responsive adenylate cyclase of microvessels and tubules isolated from rabbit kidney cortex, to oxidized PTH and PTH inhibitors, was examined. In the presence of GTP, bPTH-(1-34) stimulated both microvessel and tubule adenylate cyclase in a dose-dependent fashion and with analogous affinities (ED50 = 52 nM in the microvessels and 85 nM in the tubules). Hydrogen peroxide treatment of bPTH-(1-34) resulted in the loss of the adenylate cyclase stimulating potency in the microvessels while there was substantial enzyme activation (ED50 = 900 nM) in the tubules. Oxidized PTH inhibited the untreated PTH-stimulated adenylate cyclase, suggesting that oxidized PTH still retains an affinity for vascular receptor sites. Similar treatment of the sulfur-free PTH analog [Nle8,18, Tyr34]bPTH-(1-34)NH2, where methionines have been replaced by norleucine, had little or no effect in both fractions. In the microvessels the synthetic PTH antagonist analogs [Nle8,18, Tyr34]bPTH-(3-34)NH2 and [Tyr34]bPTH-(7-34)NH2, strongly inhibited the adenylate cyclase responses to bPTH-(1-34). No inhibition was seen in the tubules with the same molar ratios of inhibitor to native PTH. Together, these results suggest strongly that the differences in the adenylate cyclase response to various PTH fragments most likely represent a difference in the structural requirements for PTH actions between microvessels and tubules.

Adenylyl Cyclases↗
PubMed1985

Activity of phosphatases and cellular contents in glomeruli and tubules isolated from growing rat renal cortex.

The activity of acid and alkaline phosphatases was determined in glomeruli and tubules isolated from 14-day old to adult rat renal cortex. Within a nephron fraction, each phosphatase activity produced a specific pattern which was not similar to that in other fractions. In the glomeruli the acid phosphatase activity increased between 14 and 21 days of life and was always higher than in the tubules where it did not significantly change with age. By using tartrate sodium and formaldehyde it was shown that the acid phosphatase isoenzymes are distributed according to a specific pattern which does not change during maturation. The alkaline phosphatase activity in glomeruli and in tubules increases with age but is always lower in the former fraction than in the latter. Furthermore, in young as well as in adult rats, glomeruli were characterized by a higher DNA content and lower RNA and protein/DNA ratios than the corresponding tubular fragments.

Acid Phosphatase↗
PubMed1985

Isoproterenol-sensitive adenylate cyclase in glomeruli isolated from young and adult rat renal cortex.

The stimulation of the adenylate cyclase activity of isolated rat renal glomeruli by isoproterenol decreased during kidney maturation. A potentiation of the isoproterenol response by GTP was demonstrated in young and adult animals. Both KF and GPP(NH)P enhanced the enzyme activity under basal conditions in young and adult glomeruli. GTP had no significant effect upon the basal activity of the adenylate cyclase in glomeruli of 14-day old rat kidney while it had one in 21-day old and adult kidneys.

Adenylyl Cyclases↗
PubMed1984

Distribution of parathyroid hormone-sensitive adenylate cyclase in isolated rabbit renal cortex microvessels and glomeruli.

The effect of the synthetic amino-terminal fragment of bovine parathyroid hormone, bPTH-(1-34), on the adenylate cyclase of microvessels and glomeruli isolated from rabbit kidney cortex was studied in the presence and absence of guanosine triphosphate (GTP). bPTH-(1-34) stimulated the vascular and glomerular adenylate cyclase in a dose-dependent manner with apparent ED50 values of 11.5 nM and 64 nM respectively, in the absence of GTP. 10(-4)M GTP greatly amplified the vascular response to bPTH-(1-34) while, in the glomeruli, both GTP and bPTH-(1-34) had only additive effects. In the presence of GTP, vascular and glomerular apparent ED50 were 190 nM and 64 nM respectively. [Nle8, Nle18, Tyr34] -bPTH-(3-34) amide, described as a PTH antagonist, inhibited the action of bPTH-(1-34) in the microvessels and to a lesser extent in the glomeruli. PTH is therefore a potent stimulator of adenylate cyclase in rabbit renal microvessels and glomeruli, and may play a role in the regulation of renal blood flow and glomerulo-tubular feedback control.

Adenylyl Cyclases↗
PubMed1984

[Distribution of various sites of hormonal action between microvessels, glomeruli and tubules isolated from the renal cortex of rabbits].

Collagenase dispersion of rabbit kidney cortex followed by centrifugation on discontinuous sucrose gradient, allowed the simultaneous obtention of microvascular, glomerular and tubular fractions. Microscopic studies and the measurements of cellular renin activity and the muscle-specific-enzyme creatine kinase showed that these vessels were arteriolar in nature and that they contained the preglomerular arterioles. The glomerular or tubular contamination rates were assessed by means of enzymatic markers. AVP stimulated only the tubular fraction whether GTP was present or not. In the absence of GTP, beta-isoproterenol stimulated only the tubular enzyme while in the presence of GTP, the microvascular and especially the glomerular AC were also stimulated. GTP enhanced considerably the microvascular response to bPTH-(1-34) while, in the glomeruli and tubules the effects of GTP and hormones were only additive. The possible physiological significance of these results are discussed.

Animals↗
PubMed1980

Characterization of glycine-rich proteins from the ribonucleoproteins containing heterogeneous nuclear ribonucleic acid.

The salt-soluble 28 000-38 000-dalton proteins were isolated from ribonucleoproteins containing heterogeneous nuclear RNA and partially purified. They were glycine-rich proteins (22-26 mol/100) and contained a small amount of NG-dimethylarginine. Their N-terminal amino acid was blocked. Their pI was basic, extending from 6.95 to 9.20. Some 40 different polypeptides were demonstrated by combining molecular weight and pI determinations. Comparison of peptidic maps and of peptide size after trypsin and thermolysin digestion indicated the presence of only four proteins. The pattern of distribution of pI showing series of discrete major and minor bands common to two or three polypeptides of different apparent molecular weight was also compatible with the existence of four proteins and in addition supported the idea that the multiplicity of polypeptides was due to extensive posttranslational modifications.

Arginine↗