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Biomedical subjects

R H Silva

Publications and source records attributed to R H Silva.

24 records · Page 2Linked to original sources
PubMed1996

Modulation of renal kallikrein production by dietary protein in streptozotocin-induced diabetic rats.

Renal kallikrein levels and excretion rates are increased in insulin-treated diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD) diabetic rats that display renal vasoconstriction show reduced levels and excretion rates of renal kallikrein. In these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin-treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikrein excretion rate were increased compared with SD rats fed the 25% protein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 mL/min; RPF, 7.78 +/- 0.58 versus 5.14 +/- 1.03 mL/min; total kallikrein, 248 +/- 24 versus 120 +/- 30 micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excretion rate were significantly reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/- 0.09 mL/min; RPF, 5.58 +/- 0.35 versus 7.81 +/- 0.35 mL/min; total kallikrein, 119 +/- 8.3 versus 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold decrease in kallikrein mRNA levels. These findings suggest that the renal hemodynamic response to dietary protein manipulation in diabetic rats could be mediated via changes in renal kallikrein-kinin system activity.

Actins↗
PubMed1993

Thromboxane A2/prostaglandin H2 receptors in streptozotocin-induced diabetes: effects of insulin therapy in the rat.

Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are potent vasoactive and proaggregatory agents whose synthesis has been shown to be elevated in diabetes mellitus. In the present study the effects of streptozotocin (STZ)-induced uncontrolled diabetes (Severe) and insulin-treated STZ diabetes (Moderate) on TXA2/PGH2 receptor density and affinity in platelets, glomerular membranes and aortic membranes were determined using [125I]-BOP, a TXA2/PGH2 receptor agonist. The affinity and density of platelet TXA2/PGH2 receptors in Control, Moderate and Severe groups and glomerular membranes were not significantly different. However, daily insulin therapy caused significant changes in both TXA2/PGH2 receptor affinity and density of aortic membranes: Kd (nM) = 0.67 +/- 0.09, (n = 5), for Control; 0.27 +/- 0.05*, (n = 6), Moderate; and 0.74 +/- 0.16, (n = 5), Severe; Bmax (fmoles/mg protein) = 38.6 +/- 3.1, Control; 20.2 +/- 4.2*, Moderate; and 37.1 +/- 4.1, Severe: (*p < 0.05 compared to Control and Severe). Contractile responses of aortic segments to the TXA2/PGH2 receptor agonist U46619 were determined. Untreated diabetes mellitus (Severe) was associated with a decreased responsiveness of aortic segments without affecting maximum contractile responses (EC50 = 24.6 +/- 5.9* nM, (n = 10); *p < 0.05) compared to Control rats (EC50 = 11.8 +/- 1.6 nM, (n = 13)). Insulin therapy reversed the decrease seen in the Severe group to a value not different from Control (EC50 = 11.4 +/- 1.2* nM, (n = 10); *p < 0.05 compared to Severe). These results suggest that insulin therapy in the diabetic state significantly influences aortic TXA2/PGH2 receptors, as well as vascular responsiveness to TXA2/PGH2 mimetics.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Evidence for renal kinins as mediators of amino acid-induced hyperperfusion and hyperfiltration in the rat.

This study examined the role of tissue kallikrein and kinins in renal vasodilation produced by infusion of amino acids (AA). In rats fed a 9% protein diet for 2 wk, intravenous infusion of a 10% AA solution over 60-90 min reduced total renal vascular resistance and increased glomerular filtration rate (GFR) by 25-40% and renal plasma flow (RPF) by 23-30% from baseline. This was associated with a two- to threefold increase in urinary kinin excretion rate. Acute treatment of rats with aprotinin, a kallikrein inhibitor, resulted in deposition of immunoreactive aprotinin in kallikrein-containing connecting tubule cells and inhibited renal kallikrein activity by 90%. A protinin pretreatment abolished the rise in urinary kinins and prevented significant increases in GFR and RPF in response to AA. In a second group of rats pretreated with a B2 kinin receptor antagonist, [DArg Hyp3, Thi5,8 D Phe7]bradykinin, AA infusion raised urinary kinins identically as in untreated controls, but GFR and RPF responses were absent. Aprotinin or the kinin antagonist produced no consistent change in renal function in rats that were not infused with AA.AA-induced increases in kinins were not associated with an increase in renal kallikrein activity. Notably, tissue active kallikrein level fell 50% in AA-infused rats. These studies provide evidence that kinins generated in the kidney participate in mediating renal vasodilation during acute infusion of AA.

Amino Acids↗
PubMed1990

Regulation of renal kallikrein synthesis and activation by glucocorticoids.

The effects of endogenous and exogenous glucocorticoids on renal active and prokallikrein levels (ng/mg protein) and in vivo kallikrein synthesis rate were studied in the conscious rat. Within two hours after low dose methylprednisolone (MP, 0.0125 to 0.05 mg/100 g body wt), active kallikrein and prokallikrein fell (29.1 +/- 2.3 and 35.1 +/- 2.7 ng/mg protein, respectively, compared to 38.4 +/- 3.7 and 42.7 +/- 3.4 in vehicle-treated rats, P less than 0.05 or less). These changes were accompanied by a significant fall in prokallikrein synthesis rate relative to total protein synthesis. The reductions in active and prokallikrein levels were transient, dissipating by six hours. With increasing MP doses, there was further dose-dependent reduction in active kallikrein. However, prokallikrein levels increased to normal as the MP dose was increased despite continued suppression of synthesis, suggesting that prokallikrein activation was inhibited. Renal kallikrein levels were also examined in relation to changes in endogenous glucocorticoid levels. In intact rats, three hours after plasma corticosterone peaked (10 p.m.), active and prokallikrein levels were 30.2 +/- 2.9 and 27.0 +/- 1.6 ng/mg protein, respectively, compared to 36.9 +/- 2.3 and 37.2 +/- 2.6 (P less than 0.005) three hours after the corticosterone nadir (11 a.m.). Furthermore, adrenalectomy increased active and prokallikrein (47.3 +/- 4.8 and 87.3 +/- 6.0 ng/mg protein, respectively), compared to levels in intact or shamoperated rats (intact: 32.9 +/- 2.9 and 54.9 +/- 5.3 ng/mg protein, P less than 0.01 or less). Adrenalectomy also eliminated the diurnal changes in kallikrein levels seen in intact rats. These data suggest that renal prokallikrein synthesis and activation are physiologically regulated by glucocorticoids.

Animals↗
PubMedDate not supplied

Effect of ganglioside (GM1) on memory in senescent rats.

Monosialoganglioside GM1 (GM1) has been found to alleviate genetic and lesion-induced memory deficits. The purpose of this study was to investigate the effects of 7-day treatment with GM1 (50 mg/kg IP) on acquisition and retention performance of senescent rats in a passive avoidance situation. Saline-treated old rats showed a decreased performance in acquisition and retention tests as compared to saline-treated adult rats. GM1 improved both acquisition and retention performance of old animals, and there was no significant difference between GM1-treated old rats and saline-treated adult rats. These data suggest that GM1 treatment can improve memory deficits in intact senescent animals.

Aging↗