Toxicity of dimethoate on urinary hydroxyproline in rats.

The effect of the administration of three different concentrations (2.25, 1.13 and 0.56 mg/100 g body weight) of dimethoate on the urinary excretion of total, non dialysable and free hydroxyproline were studied in female albino rats. Compared to controls, the urine contents were significantly lower in higher concentration (2.25 mg/100 g body weight) of dimethoate treated rats. The results clearly indicate that the urine contents were not much affected in lower concentration (0.56 mg/100 g body weight) of dimethoate treated rats compared to the other concentrations (1.13 and 0.56 mg/100 g body weight) of dimethoate treated rats.     

Effect of high phosphorus diet on phosphorus metabolism in parathyroidectomized rats

To determine the parathyroid hormone (PTH) action on kidney and bone by high phosphorus (P) diet, this study investigated PTH/PTH-related peptide (PTHrP) receptor mRNA expression in 6-week-old parathyroidectomized (PTX) rats received constant amount of PTH. To maintain serum PTH levels equally to sham operated rats, PTX rats were constantly exposed to rPTH (1-34) and fed a control diet (0.3% P) and a high P diet (1.2% P) for 7 days, respectively. There were no significant differences in serum PTH (1-34) concentration in rats fed the control diet. In sham groups, serum PTH concentrations, both (1-84) and (1-34) fragments, were increased in rats fed the high P diet than in rats fed the control diet. Urinary excretions of P and C-terminal telopeptides of type I collagen were significantly increased in both PTX and sham rats by the high P diet. PTH/PTHrP receptor mRNA expression in kidney and femur was not changed in both PTX and sham rats by the high P diet. In conclusion, high P diet did not change PTH action in PTX rats and increased urinary excretion of P and bone resorption regardless of PTH action.     

Response of urinary hydroxyproline to dietary protein and fasting in white-tailed deer

The effects of dietary protein, fasting, and refeeding on urinary hydroxyproline of nine captive female white-tailed deer (Odocoileus virginianus) were examined from 23 February to 3 May 1984 in northern Minnesota. In the fasted group, mean hydroxyproline:creatinine (OHP:C) was greater (P less than 0.05) at week 4 compared to baseline at week 0. Between fasted deer and deer fed high protein-high energy (HPHE) and low protein-high energy (LPHE) diets, no difference in OHP:C ratios was detected during the initial 4 wk of the study. Urinary OHP:C ratios were significantly (P less than 0.05) greater in the fasted group during refeeding, concomitant with greater feed consumption and weight gain. There was also a significant (P less than 0.02) time effect in the fasted-refed group; OHP:C ratios increased during these two phases of the study. There was no difference between the HPHE and LPHE fed deer in renal OHP excretion. However, mean OHP:C ratios in yearlings (16.8 +/- 2.2) were greater (P less than 0.001) than in the adults (7.5 +/- 1.2) of those groups, indicating a higher collagen turnover rate. Urinary OHP:C shows potential as an indicator of growth and starvation, and the data presented may serve as reference values.     

Effects of dietary NaCl supplementation on bone synthesis of hydroxyproline, urinary hydroxyproline excretion and bone 45Ca uptake in the rat

High sodium chloride intakes are regarded as a risk factor for osteoporosis because they increase the obligatory urinary calcium loss and stimulate parathyroid activity. Sodium chloride loads induce osteopenia in the rat. The effect could be due to a decrease in bone formation or a rise in bone resorption. Two experiments were undertaken to study the effects of dietary NaCl supplementation on 3H-hydroxyproline synthesis and 45Ca uptake in femoral bone. Salt-treated rats excreted 1.7 times more total urinary hydroxyproline (P less than 0.001) and 2.1 times more recently labelled 3H-hydroxyproline than controls (P less than 0.02) but they did not accumulate less 3H-hydroxyproline or less 45Ca in their bones than controls. These results indicate that salt-mediated osteopenia is due to an increase in bone resorption, rather than to a decrease in bone formation.     

Excretion of urinary hydroxyproline in correlation with severity of induced osteomyelitis in rabbits.

Osteomyelitis was induced artificially by injecting Staphylococcus aureus culture in the tibiae of young rabbits. Weekly estimations of hydroxyproline in urine were done for six weeks. It was found that the osteomyelitic rabbits excreted more hydroxyproline (about 96%) two weeks after the infection in comparison to the control animals and it continued to be very high (about 138%) six weeks after the infection. The results indicate that urinary hydroxyproline reflects degradation of collagen fibers in the bone, and may be an indicator of the severity of the disease.     

Effects of aldosterone on the urinary excretion of total and non-dialyzable hydroxyproline

In order to explore the role of mineralocorticoids on collagen metabolism, the effects of aldosterone on the urinary excretion of total and non dialyzable hydroxyproline (HYPRO) was studied in rats. The administration of aldosterone in sesame oil, 75 microgram/100 g body weight to adrenalectomized rats maintained on 1% NaCl solution as drinking fluid and 1 mg of cortisone subcutaneously daily, provoked elevation of total and non dialyzable HYPRO in urine (P less than 0.001), when compared to similarly treated adrenalectomized rats receiving sesame oil but no aldosterone. Both groups showed a normal growth curve and had similar urinary excretion of creatinine. The effects of aldosterone are opposed to the known lowering effects of glucocorticoids on HYPRO excretion and may suggest an effect of aldosterone on collagen turnover. Alternatively, aldosterone may modify the metabolism or excretion of HYPRO in an opposite manner to that of glucocorticoids.     

Atrial natriuretic peptide lowers pulmonary arterial pressure in hypoxia-adapted rats

To test the hypothesis that atrial natriuretic peptide (ANP) has a direct vasodilator effect on the pulmonary vasculature that is enhanced in hypoxia-induced pulmonary hypertension in the rat, we determined the effects of ANP on mean pulmonary (MPAP) and systemic arterial pressure (MSAP) in intact conscious Sprague-Dawley rats exposed to 10% O2 or room air for 4 wk. Catheters were placed in the pulmonary artery through the right jugular vein by means of a closed-chest technique. MPAP and MSAP were monitored before and after intravenous injections of graded doses of ANP. ANP produced dose-related decreases in MPAP that were greater in the hypoxic group than in air controls. There were no significant between-group differences in the systemic depressor responses to ANP or in the ANP-induced reduction in cardiac output. ANP lowered MPAP significantly in isolated perfused lungs from both hypoxia-adapted and air control rats, and this effect was significantly greater in the hypoxic than the air control lungs. These data indicate that ANP lowers pulmonary arterial pressure in rats with hypoxia-induced pulmonary hypertension, mainly by a direct vasodilator effect on the pulmonary vasculature.     

Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation

Background

Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin.

Methodology/Principal Findings

We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3''S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3''S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL.

Conclusions

Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.