Effect of selected drugs on zinc accumulation in teeth of laboratory animals.

BACKGROUND: Zinc (Zn) is a micronutrient and essential element of life and its deficiency causes severe disorders of numerous body systems, such as immune, reproductive and central nervous system. Zinc supplementation affects wound healing and sexual development. The interactions between drugs administration and Zn level in tissues are not fully understood. The aim of the study was to demonstrate differences in Zn content in teeth of laboratory animals that have undergone pharmacological tests. METHODS: The teeth were extracted from laboratory animals after chronic administration of a non-steroidal anti-inflammatory drug (8-[4-[4-(4-chlorophenyl) piperazine-1-sulfonylphenyl]]-1-propylxanthine), a steroid anti-inflammatory drug (deoxycorticosterone) and an anti-cancer drug (oxaliplatin used acutely). The method of flame atomic absorption spectrometry was used to determine the Zn content in the teeth of the laboratory animals. RESULTS: Based on the studies conducted, the administration of the anti-inflammatory drug PSB-603 and deoxycorticosterone results in an increase in Zn accumulation in the teeth of laboratory animals, which may be indicative of the effect of anti-inflammatory drugs on the metabolism of this bioelement. Oxaliplatin has the opposite effect, after which the level of the measured bioelement in the teeth of mice depended on the administered dose. This level was on average 21.0-28.1% lower than the Zn level in the teeth of the control group. Anti-cancer drugs may interfere with Zn accumulation in the teeth and cause the removal of this metal from bone tissue. CONCLUSION: It can be assumed that the Zn content in teeth can be markedly affected by the drugs that were administrated to animals.

The flavonoid morin restores blood pressure and lipid metabolism in DOCA-salt hypertensive rats.

OBJECTIVE: This study was undertaken to investigate the antihypertensive and antihyperlipedimic potential of morin against deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Hypertension was induced in uninephrectomized rats (UNX) by weekly twice subcutaneous injection of DOCA (25 mg/kg) and 1% NaCl in the drinking water for six consecutive weeks. Morin (50 mg/kg) was administered to DOCA-salt rats orally using an intragastric tube daily for a period of 6 weeks. RESULTS: The DOCA-salt hypertensive rats showed significant elevation in mean arterial pressure (MAP), heart rate (HR) and reduction in body weight. A significant increase in the concentrations of plasma and tissue (liver, kidney, heart, and aorta) lipids such as total cholesterol, triglycerides, free fatty acids, phospholipids, plasma low-density and very low-density lipoproteins cholesterol, and a decrease in the concentration of high-density lipoprotein cholesterol were noticed in DOCA-salt hypertensive rats. Also, the levels of urinary protein and the activity of 3-hydroxy 3-methylglutaryl coenzyme A reductase in the plasma and tissues were increased, and lecithin cholesterol acyl transferase activity in the plasma was decreased in DOCA-salt rats. Morin supplementation (50 mg/kg) throughout the experimental period restored all the above parameters significantly. CONCLUSION: Morin has a potential role in attenuating severe hypertension and hyperlipedimia.

Vasorelaxant and antihypertensive effect of Cocos nucifera Linn. endocarp on isolated rat thoracic aorta and DOCA salt-induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Cocos nucifera Linn. (Arecaceae) have long been used in traditional medicine for the treatment of cardio-metabolic disorders. AIM OF THE STUDY: To evaluate the ethanolic extract of Cocos nucifera Linn. endocarp (CNE) for its vasorelaxant activity on isolated rat aortic rings and antihypertensive effects in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. MATERIALS AND METHODS: Cocos nucifera Linn. endocarp was extracted with ethanol and characterized by HPLC. CNE was examined for its in vitro vascular relaxant effects in isolated norepinephrine, phenylephrine or potassium chloride pre-contracted aortic rings (both intact endothelium and denuded). In vivo anti-hypertensive studies were conducted in DOCA salt-induced uninephrectomized male Wistar rats. RESULTS: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NNA (10µM) or ODQ (10 µM) followed by addition of contractile agonists prior to CNE significantly blocked the CNE-induced relaxation. Indomethacin (10µM) and atropine (1 µM) partially blocked the relaxation, whereas glibenclamide (10 µM) did not alter it. CNE significantly reduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from 185.3 ± 4.7 mmHg to 145.6±6.1 mmHg). The activities observed were supported by the polyphenols, viz. chlorogenic acid, vanillic acid and ferulic acid identified in the extract. CONCLUSIONS: These findings reveal that the vasorelaxant and antihypertensive effects of CNE, through nitric oxide production in a concentration and endothelium-dependent manner, is due to direct activation of nitric oxide/guanylate cyclase pathway, stimulation of muscarinic receptors and/or via cyclooxygenase pathway.

Dietary sesamin suppresses aortic NADPH oxidase in DOCA salt hypertensive rats.

1. Dietary sesamin, a sesame lignan, is known to suppress the development of experimental hypertension in rats partly through its inhibitory effect on vascular O(2)(-) production. Therefore, in the present study, we examined whether sesamin feeding had any effect on vascular NADPH oxidase using aortas from deoxycorticosterone acetate (DOCA) salt hypertensive rats. 2. After a 5 week feeding and treatment period, aortic O(2)(-) production and NADPH oxidase activity were measured using the lucigenin assay. Reverse transcription-polymerase chain reaction was performed to analyse aortic expression of NADPH oxidase subunit (p22phox, gp91phox, Nox1 and Nox4) mRNA. 3. Sesamin feeding markedly suppressed DOCA salt-induced hypertension and significantly decreased aortic O(2)(-) production. DOCA salt treatment increased NADPH oxidase activity and elevated aortic mRNA expression of p22phox, gp91phox, Nox1 and Nox4. Sesamin feeding abolished the increase in NADPH oxidase activity and, furthermore, significantly suppressed increases in p22phox, gp91phox and Nox1 mRNA expression. 4. In conclusion, dietary sesamin prevented DOCA salt-induced increases in NADPH oxidase activity and subunit mRNA expression. These effects seem to be involved in the anti-oxidant and antihypertensive effects of sesamin.

Enhanced depressor effect of centrally administered high-calcium solution in salt-loaded experimental hypertension.

The depressor effect by oral calcium supplementation is known to be more pronounced in salt-dependent than in renin-dependent hypertension. This study was conducted to investigate the role of central calcium on two different pathophysiologic subtypes of experimental hypertension; (a) salt-dependent, deoxycorticosterone acetate-salt hypertensive rats (DOCA), and (b) renin-dependent, 2-kidney, 1 clip (2-K, 1C) hypertensive rats. In DOCA (n = 10), high-calcium solution (Ca+2, 65.2 mM, 10 microl) given centrally (i.c.v.) elicited a marked decrease in mean blood pressure (MBP; 170 +/- 4 to 138 +/- 5 mm Hg, p < 0.01) with a decrease in heart rate (HR; 390 +/- 18 to 344 +/- 17 beats/min, p < 0.05) lasting for 40 min. In 2-K, 1C (n = 10), high-Ca2+ i.c.v. showed a lesser decrease in MBP (178 +/- 4 to 171 +/- 5 mm Hg) and HR (419 +/- 10 to 395 +/- 12 beats/min) with shorter duration (for 20 min) than in DOCA. This significant depressor and bradycardic response to Ca2+ i.c.v. observed in DOCA was dose dependent at Ca2+ concentrations between 65.2 and 130.4 mM. In DOCA, high Ca2+ i.c.v. reduced the plasma noradrenaline (Nad) concentration significantly (479 +/- 81 to 319 +/- 62 pg/ml, p < 0.05). These results suggest that central Ca2+ plays a more important role in regulating sympathetic nerve activity and BP in salt-dependent than in renin-dependent experimental hypertension.

Effects of desoxycorticosterone pivalate administration on blood pressure in dogs with primary hypoadrenocorticism.

A study was designed to evaluate the effects of desoxycorticosterone pivalate (DOCP) on blood pressure in 8 dogs with primary hypoadrenocorticism, and to attempt to identify other factors that might suggest overdosage of the drug. In 4 dogs, primary hypoadrenocorticism had been diagnosed immediately before entry of the dog into the study, and the dogs had not received any mineralocorticoid supplementation. In the other 4 dogs, primary hypoadrenocorticism had been diagnosed 1 to 6 years previously, and dogs were being treated with DOCP at the time of entry into the study. In all 8 dogs, DOCP (2.2 mg/kg of body weight, IM) was administered on days 0, 30, 60, and 90 of the study; each dog was examined on days 0, 30, 60, 75, 90, and 105. At the time of each visit, a medical history was obtained, a complete physical examination and serum biochemical analyses were performed, and body weight and blood pressure were measured. Doppler-shift ultrasonic sphygmomanometry was used to indirectly record systemic systolic and diastolic pressures. None of the dogs developed hypernatremia or hypokalemia or any clinical signs suggestive of hypoadrenocorticism during the study. However, in 6 dogs (3 that had not been previously treated with mineralocorticoids and 3 that had been), there was a significant increase in body weight over the course of the study. Compared with baseline (day 0) arterial blood pressure, neither systolic nor diastolic blood pressure was significantly increased during the study, and all systolic and diastolic blood pressure measurements were within reference ranges at all evaluation times.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypotensive action of taurine in DOCA-salt rats--involvement of sympathoadrenal inhibition and endogenous opiate.

We studied the roles of the sympathoadrenal system and endogenous opiate in the antihypertensive effects of supplementation of dietary taurine, a sulfur amino acid, in deoxycorticosterone acetate (DOCA)-salt rats. Supplementation of 1% taurine in drinking water for 2 weeks was found to prevent the increase in systolic blood pressure of DOCA-salt rats (116 +/- 2 vs 138 +/- 2 mmHg, p less than 0.01), but failed to effect the systolic blood pressure of vehicle-treated control rats (115 +/- 2 vs 112 +/- 3 mmHg), taurine supplementation restored to normal increased plasma norepinephrine (326 +/- 32 vs 531 +/- 67 pg/ml, p less than 0.01) and epinephrine (204 +/- 19 vs 304 +/- 43 pg/ml, p less than 0.05) concentrations in DOCA-salt rats, but had no effect on norepinephrine (346 +/- 23 vs 338 +/- 33 pg/ml) or epinephrine (198 +/- 17 vs 224 +/- 26 pg/ml) concentrations in control rats. Accordingly, the increased epinephrine content in the adrenals of DOCA-salt rats was normalized with the supplementation of taurine, associated with a markedly increased adrenal taurine content. In conscious rats, moreover, intraperitoneal injection of naloxone (2 mg/kg), a specific opiate antagonist, increased systolic blood pressure only in taurine-supplemented DOCA-salt rats. Evidence presented suggests, therefore, that both the suppression of the increased sympathoadrenal activity and the activation of endogenous opiate might contribute to the antihypertensive effect of taurine in DOCA-salt rats.

Effect of nitrendipine on blood pressure, plasma renin, and exchangeable sodium in DOC-salt hypertension in the rat.

Desoxycorticosterone-salt (DOC-salt) hypertension in the rat can be prevented by administration of nitrendipine. We have studied the effect of nitrendipine on exchangeable body sodium (NaE) in this model. Eighteen male Sprague-Dawley rats had a left nephrectomy and after 14 days received subcutaneous injections of deoxycorticosterone (Percorten, CIBA) 12.5 mg three times weekly for 4 weeks and were given 22Na-labeled 1% saline plus 0.2% KCl to drink. They were fed a sodium-free diet. NaE, systolic blood pressure, and body weight were measured weekly. The animals were divided into two groups of nine, one group being given subcutaneous nitrendipine 5 mg/kg twice daily, while the control group was given vehicle only. Blood samples from conscious animals were drawn at the start and at the end of the study for measurement of plasma renin concentration (PRC) and haematocrit, and at the end for atrial natriuretic peptide (ANP) measurement. Twenty-four hour urine was collected at the end of the study from eight rats of each group, and urine and blood samples were taken for biochemical analysis. In the control rats, blood pressure rose from an initial mean of 140.6 +/- 1.7 (SEM) mm Hg to 187.2 +/- 6.5 (p less than 0.001) at week 4. In the nitrendipine-treated rats, blood pressure fell from 143.9 +/- 2 at week 0 to 127.2 +/- 3.3 mm Hg at week 4 (p less than 0.001). However, body weight rose similarly in both groups and there was no difference in NaE between the groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

KCl inhibits hypothalamic activity to attenuate hypertension in DOCA-salt rats.

Potassium supplementation attenuated the development of hypertension in DOCA-salt rats but did not affect blood pressure in control rats. However, it caused a decrease in body weight in both groups of rats. Sympathetic nerve and pressor responses either to electrical stimulation of the hypothalamus or to intracisternal injections of hypertonic NaCl were enhanced in DOCA-salt rats but were normalized by KCl supplementation. Since the pressor responses to injected norepinephrine or tyramine remained unaltered by KCl treatment, a peripheral inhibition of cardiovascular reactivity was considered unlikely. Pretreatment with methyclothiazide also attenuated the elevation in blood pressure but did not affect the responsiveness to hypothalamic stimulation; hence increased natriuresis or diuresis alone could not account for the effects induced by KCl. These findings are consistent with the conclusion that KCl supplementation attenuates the development of DOCA-salt hypertension in rats by acting on the central nervous system to reduce sympathetic output.

Prevention of DOCA-salt hypertension with the calcium blocker nitrendipine.

Mononephrectomized female rats on a high sodium intake developed hypertension, hypokalemia, enlarged hearts and kidneys and slight adrenal involution under deoxycorticosterone treatment. Simultaneous administration of nitrendipine (5 mg/kg twice daily) completely prevented hypertension and reduced but did not abolish cardiac enlargement. There was no effect of the calcium slow-channel inhibitor on kidney enlargement, adrenal atrophy or hypokalemia. The ability of the steroid to produce cardiomegaly in the absence of an elevated blood pressure to account for it, tends to confirm the suggestion of other investigators that the steroid may have that effect by a mechanism not involving blood pressure elevation.