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C Caramelo

Publications and source records attributed to C Caramelo.

At least 109 records · Page 6Linked to original sources
PubMed1988

Mechanisms of the vascular effect of pressor hormones.

There exists a considerable gap between the recognition of the effects of pressor hormones and the understanding of their mechanisms. Studies are necessary to provide a more accurate basis for potential therapeutic interventions on the hormonal mechanisms of hyper- and hypotensive states. From recent and previous experimental results, a modified model of vascular smooth muscle cell activation is emerging. In this model, contraction is a complex process involving Ca2+ release, protein kinase C and ionic channel activation and modification in pH and energy metabolism. The combined action of these processes is necessary for the full expression of the contractile response.

Angiotensin II↗
PubMed1988

Mechanism of cellular effect of phorbol esters on action of arginine vasopressin and angiotensin II on rat vascular smooth muscle cells in culture.

The inhibitory effect of phorbol-12-myristate-13-acetate (PMA) on the Ca2+-mobilization mechanisms by arginine vasopressin (AVP) and angiotensin II (AII) was analysed in rat vascular smooth muscle cells (VSMC) in culture. PMA inhibited the Ca2+-mobilizing effect of both AVP and AII in a dose-dependent manner, including the rise in cytosolic free Ca2+ ( [Ca2+]i) and Ca2+ efflux. In addition, inositol trisphosphate (IP3) production induced by AVP or AII was more than 50% reduced by PMA. The involvement of protein kinase C was implicated by the diminution of the PMA effect by the specific protein kinase C inhibitor isoquinoline-sulphonyl-O-2-methylpiperazine (H7) and the lack of effect of an inactive phorbol. Thus, these results suggest that there is a blocking site that is common or similar for both AVP and AII signal transduction, and that it is a substrate for protein kinase C. This blocking action of protein kinase C occurred at least in part by inhibition of IP3 production and, subsequently, a reduction in cytosolic Ca2+ release. In the presence of ionomycin, which produces an increase in [Ca2+]i that is not altered by PMA, 45Ca2+ efflux was increased instead of inhibited by PMA, thus suggesting that protein kinase C activation also stimulates a Ca2+-extrusion mechanism in VSMC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Protein kinase C activity in compensatory kidney growth.

Very little information exists about the intracellular mechanisms mediating remnant kidney hypertrophy after reduction of renal mass. The present experiments demonstrate that the activity of a key enzyme in cellular proliferation, protein kinase C, is enhanced in the kidney during post-uninephrectomy hypertrophy. As additional evidence of "in vivo" enzyme activation, the enzyme activity migrates from the cytosolic to the particulate fraction of the cells and the number of sites of phorbol dibutyrate binding is enhanced in kidney membranes 24 hr after contralateral nephrectomy. The stimulation of the enzyme is higher than the increase in kidney weight, although both phenomena are linearly related.

Animals↗
PubMed1988

Tubular hypermetabolism as a factor in the progression of chronic renal failure.

Thus, in summary, we hypothesize that nephron loss by a time-limited insult (eg, an acute immunological insult, surgical removal of five sixths of normal nephrons) may cause events in the tubules of the remaining nephrons that contribute substantially, though not exclusively, to the inexorable progression to ESRD. Specifically, hypermetabolism in the remaining tubules as assessed by oxygen consumption and ATP synthesis rates has been found to occur. This hypermetabolism in residual nephrons appears to be due to the known increased sodium transport per nephron, but nonsodium transport events also appear to be involved. With respect to the latter phenomenon, we propose that an increase in growth factor response per tubule, as a mechanism of renal hypertrophy, activates the DAG----protein kinase C----Na/H antiporter system. We have evidence in support of this sequence of events by the demonstration of a two-fold increase in membrane (particulate) protein kinase C within 24 hours after removal of the contralateral kidney and an increase in intracellular pH as assessed by NMR spectroscopy. Activation of the Na/H antiporter not only leads to proton extrusion and cellular alkalinization, which may activate cellular alkalinization, which may activate cellular enzymes such as phospholipases, but also increases intracellular Na concentration, thereby further increasing Na/K-ATPase, ATP use, and enhancing ATP synthesis. The increase in mitochondrial oxygen consumption, which accompanies the enhanced ATP synthesis, would be expected to be associated with increased oxygen radicle generation. If the tissue scavengers of oxygen radicles are not sufficient to scavenge the increase in oxygen radicles, then lipid peroxidation and tissue damage will occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Vascular reactivity to norepinephrine in rats with cirrhosis of the liver.

Vascular reactivity to norepinephrine was studied in rats with early cirrhosis of the liver and in control rats. Cirrhotic rats showed water and sodium retention but not ascites. Studies were performed in whole animals, isolated hindquarters, and isolated femoral arteries. Plasma catecholamine levels were measured by radioenzymoassay and their urinary metabolites by gas-liquid chromatography. Plasma norepinephrine was 331 +/- 49 pg/mL (mean +/- SEM) in control rats and 371 +/- 66 pg/mL in cirrhotic animals (p greater than 0.05). No differences in plasma epinephrine or dopamine were observed. Urinary excretion of catecholamine metabolites was increased in cirrhotic rats. These data suggest a moderate activation of the sympathetic nervous system. In basal conditions, cirrhotic rats showed lower mean arterial pressure than controls (101 +/- 4 vs. 116 +/- 4 mmHg (1 mmHg = 133.3 Pa); p less than 0.01). However, perfused hindlimb resistance was similar in cirrhotic and in control animals. In the whole animal and in the perfused hindquarter, the contractile response to norepinephrine was similar for control and for cirrhotic rats. The contractile response to norepinephrine exhibited by isolated femoral arteries was similar in those from cirrhotic and control rats. This indicates that the peripheral vascular bed has a well-maintained ability to constrict in response to norepinephrine, suggesting that circulatory abnormalities in early experimental cirrhosis are not caused by refractoriness of the vascular smooth muscle to norepinephrine.

Animals↗
PubMed1988

ANF inhibits vasopressin-induced Ca2+ mobilization and contraction in glomerular mesangial cells.

It has been suggested that atrial natriuretic factor (ANF) may increase glomerular filtration rate (GFR) via alteration of the glomerular ultrafiltration area, which is at least in part regulated by the contractile state of mesangial cells. The present study therefore investigated the effect of ANF (atriopeptin III) on arginine vasopressin (AVP)-induced Ca2+ mobilization and contraction in cultured rat mesangial cells. AVP (10(-8) M) increased intracellular Ca2+ ([ Ca2+]i) as measured by the quin2 method (142.1 +/- 3.7 vs. 297.9 +/- 8.9 nM, P less than 0.001). This effect, however, was diminished by 10(-8) M ANF (297.9 +/- 8.9 vs. 233.1 +/- 9.3 nM, P less than 0.0025). ANF alone did not affect basal [Ca2+]i. AVP-stimulated 45Ca2+ efflux (cpm.mg prot-1.30 s-1) from mesangial cells within 30 s (1,432 +/- 70 basal vs. 2,751 +/- 287 AVP at 30 s, P less than 0.001). This effect of AVP on 45Ca2+ efflux was also inhibited by ANF (1,403 +/- 62 basal vs. 1,584 +/- 87 AVP and ANF, NS); ANF alone had no effect on spontaneous 45Ca2+ efflux. Furthermore, ANF inhibited AVP-induced 45Ca2+ uptake, which is purportedly one of the major determinants of the sustained phase of cell contraction. Cell contraction was assessed by digital imaging analysis. AVP (10(-7) M) caused contraction of 33.8 +/- 2.0% of the cells, but the contractile response decreased to 20.7 +/- 2.3% in the presence of 10(-9) M ANF and was virtually abolished in the presence of 10(-8) M ANF. Guanosine 3',5'-cyclic monophosphate (cGMP) has been proposed as the second messenger for ANF. ANF (10(-7) M) stimulated cGMP production significantly (0.54 +/- 0.12 vs. 22.30 +/- 5.91 pmol.mg prot-1.10 min-1, P less than 0.01), but it had no effect on cGMP at concentrations of 10(-8) M and below. 8-Bromo-cGMP (8-BrcGMP) attenuated the stimulatory effect of AVP on [Ca2+]i, 45Ca2+ efflux, and 45Ca2+ uptake. AVP-induced cell contraction was also decreased in the presence of 2 mM 8-BrcGMP (33.8 +/- 2.0% vs. 18.8 +/- 2.6%, P less than 0.005). The present results suggest that ANF may increase GFR in part by blocking the cellular action of AVP and possibly other vasoconstrictors on glomerular mesangial cells, thus affecting glomerular filtration area. A role of cGMP as second messenger for ANF is possible, but it appears unlikely to be the only mediator for the effects of ANF.

Animals↗
PubMed1988

Interaction of atriopeptin III and vasopressin on calcium kinetics and contraction of aortic smooth muscle cells.

The cellular mechanism of the vasodilatory action of atriopeptin III (APIII) on vasopressin (AVP)-induced Ca2+ mobilization and cell shape change in cultured vascular smooth muscle cells (VSMC) was studied. APIII (10(-8) M) attenuated the increase of intracellular free Ca2+, [Ca2+]i, induced by 10(-8) M AVP (234.0 +/- 14.8 vs. 310.0 +/- 28.4 nM, P less than 0.01). Similar results were obtained in 45Ca2+ efflux experiments. APIII (10(-7) M), however, did not alter AVP-induced inositol trisphosphate (IP3) production, although the levels of inositol-1-phosphate were significantly reduced. The effect of APIII to block or attenuate AVP-induced Ca2+ mobilization was associated with an inhibition of AVP-stimulated cell shape change. The effect of atrial natriuretic factor (ANF) on cell shape, however, occurred at lower ANF concentrations than the effect on the Ca2+ mobilization. APIII stimulated production of cyclic guanosine monophosphate (cGMP) in VSMC. The effect of APIII on AVP-stimulated Ca2+ mobilization was partially mimicked by the stable nucleotide 8-bromo cGMP and was not affected by the soluble guanylate cyclase inhibitor, methylene blue (10(-4) M). These results suggest that APIII exerts its vasodilatory effect, in part, by interference with vasopressor-stimulated Ca2+ mobilization in vascular smooth muscle cells, perhaps by stimulating particulate guanylate cyclase and cGMP. However, an effect of ANF on the contractile mechanism at a site independent of Ca2+ release is also suggested by the present results.

Animals↗
PubMed1988

Effect of intrarenal infusion of synthetic PAF-acether in dogs.

The effect of intrarenal infusion of PAF-acether was studied in dogs. PAF-acether infusions caused a dose-dependent decrease in glomerular filtration rate, renal blood flow and urinary flow and electrolyte excretion, without significant changes in mean arterial pressures. In addition, the higher doses used caused also increases in packed cell volume, and decreases in plasma proteins and leukocyte and platelet count, whereas the lower doses did not elicit those changes. These data suggest that PAF-acether causes an impairment in renal function which is in part mediated by vasoactive substances released from platelets and leukocytes.

Animals↗
PubMed1988

Haemodynamic effects of angiotensin II in conscious, non-ascitic cirrhotic rats.

The effect of angiotensin II (AII) on systemic and regional haemodynamics was studied in 18 control and 18 cirrhotic, non-ascitic conscious rats (CCl4/phenobarbital model). Cirrhotic rats were found to retain sodium and to have normal plasma renin and plasma aldosterone concentrations when compared with control animals. Cirrhotic rats showed an enhanced cardiac output (34.4 +/- 0.5 vs. 27.5 +/- 2.0 ml/min in controls) and decreased peripheral resistances (2.96 +/- 0.25 vs. 3.95 +/- 0.31 mm Hg/min/100 g/ml in controls) under basal conditions. When AII was administered cardiac output decreased by 10.7 +/- 1.2% in cirrhotic rats, whereas it increased in control animals (11.2 +/- 2%, p less than 0.005). The AII-induced increase in arterial pressure was lower in cirrhotic than in control rats. The renal blood supply was particularly impaired by AII in cirrhotics, with a maintained flow to other organs (muscle, testes). It is concluded that the response to AII is disturbed in rats with hepatic cirrhosis even in a stage without ascites and with plasma renin and aldosterone concentrations similar to those of control animals.

Aldosterone↗
PubMed1987

Increased levels of platelet-activating factor in blood from patients with cirrhosis of the liver.

The levels of platelet-activating factor (paf-acether) were measured in blood and ascitic fluid from cirrhotic patients and in blood from a group of controls, using a recently described technique for extraction and measurement. In addition, activity of acetylhydrolase, the main catabolic enzyme for paf-acether, was also measured. The highest levels of paf-acether in blood were found in decompensated cirrhotics (1.78 +/- 0.62 ng ml-1; mean +/- SD, n = 8). Compensated cirrhotics showed lower blood values (0.79 +/- 0.21, n = 4), but higher than controls (0.20 +/- 0.04, n = 12). Paf-acether levels in ascitic fluid were similar to those of blood. Values of acetylhydrolase in serum were similar in all the groups studied (3.0 +/- 0.4 in cirrhotics vs. 2.3 +/- 0.4 nmol min-1 mg-1 of protein in controls). These data suggest an enhanced production of paf-acether in cirrhotic patients rather than a decreased catabolism. High levels of paf-acether in blood could be involved in the impaired haemodynamics of cirrhotic patients and in their renal function alterations.

Adult↗
PubMed1986

Effects of the platelet-activating factor antagonist BN 52021 on the hemodynamics of rats with experimental cirrhosis of the liver.

Previous studies from this laboratory have shown that rats with experimental cirrhosis of the liver induced by the combined administration of oral phenobarbital and inhaled carbon tetrachloride show an hyperdynamic status with enhanced cardiac output (CO), and decreased mean arterial pressure (MAP) and peripheral vascular resistance (PVR). Cirrhotic rats also showed an increased vascular permeability. All these phenomena are similar to some of the known effects of the systemic infusion of low doses of synthetic platelet-activating factor into the systemic circulation of normal rats. The measurement of the levels of platelet-activating factor in samples of blood demonstrated significantly higher levels in cirrhotic (2.65 +/- 0.39; n = 10) than in control rats (1.50 +/- 0.57 ng/ml; n = 10; p less than 0.05). The hemodynamic changes induced by the intravenous injection of the platelet-activating factor receptor antagonist BN 52021 (5 mg/kg body weight) have been measured in 10 control and 10 cirrhotic male Wistar rats, using a radioactive microsphere technique. BN 52021 induced no significant hemodynamic changes in control animals. However, in cirrhotic animals it induced a significant decrease in CO with increase in PVR. MAP increased slightly but not significantly. From these data it can be deduced that platelet-activating factor plays a role in the hemodynamic derangement shown by cirrhotic rats and that these derangement can be reversed by BN 52021, a highly selective antagonist of the platelet-activating factor receptor.

Animals↗
PubMed1986

Lack of a direct regulatory effect of atrial natriuretic factor on prostaglandins and renin release by isolated rat glomeruli.

We have tested the direct regulatory effect of synthetic Atrial Natriuretic Peptide (ANP, 8-33aa) on prostaglandins and renin release by isolated rat glomeruli. Variable incubation times and doses of ANP did not modify the rate of PGE2, PGF2a and TXB2 production. Similar results were obtained for renin release. These data do not support a role for ANP in the regulation of prostaglandins and renin release by rat glomeruli.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Systemic and regional haemodynamic effects of a synthetic atrial natriuretic peptide in conscious rats.

The effect of the intravenous injection of synthetic atrial natriuretic peptide (ANP, 2 micrograms) on systemic haemodynamics and blood flow to several organs has been studied in conscious rats by the radioactive microsphere technique. ANP induced a 540% increase in sodium excretion and a 310% increase in urine flow. Mean arterial pressure decreased by 21 mmHg and the peripheral resistances decreased by 26%, without significant changes in cardiac output. Renal blood flow increased by 37.7% and small intestine and portal blood flow increased by 39% and by 28% respectively. No other alterations in organ blood flows were observed. From these data it can be concluded that atrial natriuretic peptide shows acute vascular relaxant properties, which seem to be specific for renal and mesenteric territories.

Animals↗
PubMed1985

Lack of effect of synthetic atrial natriuretic factor on rubidium uptake by human erythrocytes.

The effect of synthetic atrial natriuretic factor on the ouabain-sensitive and the furosemide-sensitive rubidium uptake by human erythrocytes has been studied. This peptide with potent diuretic and natriuretic effects did not affect any rubidium uptake system at concentrations of 10(-7) and 10(-9) M. These results do not support that the natriuretic effect is based on the inhibition of active transport systems in the renal tubules.

Atrial Natriuretic Factor↗
PubMed1985

Systemic and splanchnic hemodynamic disturbances in conscious rats with experimental liver cirrhosis without ascites.

Rats with CCl4-induced cirrhosis of the liver show histological and clinical features that closely resemble those of the disease in humans. Metabolic cages were used and hemodynamic studies (15-micrograms radioactive microspheres) were performed on 10 conscious, nonascitic, cirrhotic rats and in 10 control rats. Compared with control animals, cirrhotic rats showed lower sodium excretion (0.80 +/- 0.07 vs. 1.01 +/- 0.07 meq/day), total solute excretion (12.52 +/- 0.79 vs. 19.38 +/- 3.7 mosmol/day), and increased aldosterone excretion. No differences were observed in urinary epinephrine and norepinephrine excretion. Cirrhotic rats showed also slight hypotension, increased cardiac output (48.97 +/- 3.94 vs. 26.97 +/- 2.3 ml X min-1 X 100 g-1) without tachycardia, and decreased total peripheral resistance, which was mainly attributed to reduced renal and skeletal muscle resistances with increased blood flow throughout these areas. Cirrhotic rats showed increased hepatic vascular resistances by both portal and arterial inputs with portal hypertension (16.15 +/- 1.01 vs. 9.60 +/- 0.77 cmH2O) but without differences in total hepatic blood flow or portal-systemic shunt rate with respect to control rats. Plasma renin content was not significantly different between the groups of rats. From these data it can be concluded that nonascitic, cirrhotic rats show a hyperdynamic circulatory state, which seems to be caused by a peripheral vasodilation of unknown mechanism; portal-systemic shunting does not seem to be a necessary condition for the hyperdynamic status at this early stage of the hemodynamic disturbances.

Animals↗
PubMed1985

Effect of chronic and progressive increase of portal venous pressure on renal handling of water and electrolytes in rats.

Systemic and splanchnic hemodynamics and the changes in renal function induced by saline infusion (3% body weight) were studied in rats with a chronic and progressive model of portal hypertension (CPH) and in a control group. CPH rats showed a hyperdynamic circulatory status with increased cardiac output, decreased total peripheral resistances, and decreased portal inflow. Portal hypertension was accompanied by intrahepatic hypertension. Clearance studies revealed that in basal conditions CPH rats showed lower glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow, and potassium excretion than control rats, while the difference in Na and Cl excretion was not statistically significant. After saline infusion (3% body weight, 15 ml/h), differences in GFR and RPF became nonsignificant, but CPH rats showed lower Na, Cl and osmolar excretion and urinary flow than control rats. In basal conditions, plasma renin content was higher in CPH than in control rats, and decreased in both groups after volume expansion, the difference then being not statistically significant. These results demonstrate that chronic portal hypertension results in impairment of GFR, RPF and renal handling of water and electrolytes and suggest the involvement of a hepatorenal sympathetic reflex in these alterations. This reflex could be stimulated by the increase in intrahepatic pressure rather than by portal hypertension per se.

Animals↗
PubMed1984

Presence of platelet-activating factor in blood from humans and experimental animals. Its absence in anephric individuals.

Blood from humans and experimental animals was examined for the presence of platelet-activating factor. The procedure included a rapid extraction of the samples and a purification of the lipid content by thin layer chromatography. The chemical characterization was performed by phospholipases' treatment and high performance liquid chromatography. Rats contained the highest concentrations of platelet-activating factor and rabbits the lowest. Five anephric patients undergoing support hemodialysis had undetectable blood levels and the same finding was observed in six rats in which surgical nephrectomy was performed. Based on these data we suggest: 1) Low amounts of platelet-activating factor can be present in blood under normal conditions. 2) Kidney tissue seems to play a role in the formation of the platelet-activating factor that can be detected in blood under these conditions.

Animals↗