Biomedical subjects

I A Medeiros

Publications and source records attributed to I A Medeiros.

17 recordsLinked to original sources

PubMed2006

Endothelium-derived factors and k+ channels are involved in the vasorelaxation induced by Sida cordifolia L. in the rat superior mesenteric artery.

The vasorelaxantion of the aqueous fraction of the hydroalcoholic extract of the Sida cordifolia leaves (AFSC) was evaluated in this work. In rat superior mesenteric artery, AFSC (3-1000 microg/mL) induced relaxation of phenylephrine-induced contractions. This effect was significantly attenuated after removal of the endothelium, after atropine (1 microM), L-NAME (100 microM), indomethacin (10 microM), high K+ (20 mM), tetraethylammonium (1 microM), a K(Ca) blocker, apamin (1 microM), a SK(Ca) blocker and ChTX (0.1 microM), a BK(Ca) blocker, however, it was not affected after glibenclamide (10 microM), an KATP blocker, and 4-aminopyridine (1 microM), a Kv blocker. ChTX (0.1 microM) was able to induce an additional inhibition of the vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin. The vasorelaxation induced by AFSC in the presence of L-NAME plus indomethacin plus ChTX was not different from that induced by AFSC in rings without endothelium. In conclusion, the results show that endothelium-derived factors (mainly NO, PGI2) and K+ channels (BK(Ca) and SK(Ca)) play a crucial role in the vasorelaxation induced by AFSC in the rat superior mesenteric artery.

Animals↗

PubMed2005

Cardiovascular effects of Sida cordifolia leaves extract in rats.

The cardiovascular activity of the aqueous fraction of the hydroalcoholic extract of Sida cordifolia leaves (AFSC) was evaluated. In normotensive non-anaesthetized rats was observed that AFSC (5, 10, 20, 30 and 40 mg/kg, i.v.) induced hypotension (6 +/- 2%; 8 +/- 2%; 11 +/- 2%; 19 +/- 3% and 33 +/- 3%, respectively) and bradycardia (0.3 +/- 3%; 13 +/- 4%; 38 +/- 6%; 64 +/- 7% and 80 +/- 5%, respectively). Hypotensive response was completely abolished after atropine (2 mg/kg; i.v.) but potentialized after hexamethonium (20 mg/kg; i.v.) (12 +/- 2%; 21 +/- 5%; 28 +/- 3%; 32 +/- 2% and 32 +/- 3%, respectively), while bradycardic response was completely abolished after atropine (2 mg/kg; i.v.) and attenuated with hexamethonium (20 mg/kg; i.v.) (1 +/- 0.3%; 5 +/- 1%; 7 +/- 1%; 7 +/- 1% and 10 +/- 1%, respectively). In hexamethonium treated rats, L-NAME significantly attenuated the hypotensive response (9 +/- 2%; 14 +/- 1%; 16 +/- 1%; 16 +/- 2% and 22 +/- 3%, respectively). In normotensive anaesthetized and vagotomized rats, hypotensive and bradycardic responses were significantly attenuated (0.5 +/- 0.2%; 1 +/- 0.4%; 3 +/- 0.6%; 4 +/- 0.8% and 6 +/- 1%, respectively, n = 6, and 7 +/- 2%; 12 +/- 5%; 15 +/- 2%, 17 +/- 2% and 25 +/- 3%, respectively). The anaesthesia with sodium thiopental did not affect the AFSC-induced responses when compared with those induced in non-anaesthetized rats (data not showed). In conclusion, the results obtained so far show that AFSC produce hypotension and bradycardia, mainly due to a direct stimulation of the endothelial vascular muscarinic receptor and indirect cardiac muscarinic activation, respectively.

Anesthesia↗

PubMed2005

Anorectic and behavioural effects of chronic Cissampelos sympodialis treatment in female and male rats.

Male and female rats were treated daily for 13 weeks with an ethanol extract of Cissampelos sympodialis leaves (9, 45 and 225 mg[sol ]kg). The food consumption, body weight and behavioural effects in the open-field test were evaluated by weekly monitoring. The results showed that the extract chronic treatment in female rats (45 and 225 mg[sol ]kg) reduced significantly the food intake and the body weight, and produced several alterations in the open-field test. These findings indicate that repeated oral administration of the extract may produce a sex-dependent difference in anoretic and behavioural effects.

Administration, Oral↗

PubMed2004

Calcium antagonism and the vasorelaxation of the rat aorta induced by rotundifolone.

The vasorelaxing activity of rotundifolone (ROT), a major constituent (63.5%) of the essential oil of Mentha x villosa, was tested in male Wistar rats (300-350 g). In isolated rat aortic rings, increasing ROT concentrations (0.3, 1, 10, 100, 300, and 500 microg/ml) inhibited the contractile effects of 1 microM phenylephrine and of 80 or 30 mM KCl (IC50 values, reported as means +/- SEM = 184 +/- 6, 185 +/- 3 and 188 +/- 19 microg/ml, N = 6, respectively). In aortic rings pre-contracted with 1 microM phenylephrine, the smooth muscle-relaxant activity of ROT was inhibited by removal of the vascular endothelium (IC50 value = 235 +/- 7 microg/ml, N = 6). Furthermore, ROT inhibited (pD2 = 6.04, N = 6) the CaCl2-induced contraction in depolarizing medium in a concentration-dependent manner. In Ca2+-free solution, ROT inhibited 1 microM phenylephrine-induced contraction in a concentration-dependent manner and did not modify the phasic contractile response evoked by caffeine (20 mM). In conclusion, in the present study we have shown that ROT produces an endothelium-independent vasorelaxing effect in the rat aorta. The results further indicated that in the rat aorta ROT is able to induce vasorelaxation, at least in part, by inhibiting both: a) voltage-dependent Ca2 channels, and b) intracellular Ca2+ release selectively due to inositol 1,4,5-triphosphate activation. Additional studies are required to elucidate the mechanisms underlying ROT-induced relaxation.

Animals↗

PubMed2004

Calcium mobilization as the endothelium-independent mechanism of action involved in the vasorelaxant response induced by the aqueous fraction of the ethanol extract of Albizia inopinata G. P. Lewis (AFL) in the rat aorta.

In a previous work, we demonstrated that, in normotensive rats, AFL induced a marked hypotension due to a decrease in total peripheral resistances (TPR), partially secondary to the release of NO by the endothelium. NO did not, however, account for the total vasodilation produced by AFL in these rats. The aim of this study was to determine the involvement of the intracellular calcium mobilization in the vasorelaxant action induced by AFL in the rat aorta. In aorta of normotensive rats AFL (10, 20, 40 and 80 microg/ml) inhibited the sustained contractions induced by KCl (80 and 30 mM) and phenylephrine (Phe, 1 microM) with similar IC50 values (54 +/- 6, 52 +/- 4 and 65 +/- 4 microg/ml, respectively). The relaxing response induced by AFL against Phe-induced contractions was modified significantly by the endothelium removal (IC50 = 132 +/- 23 and 65 +/- 4 microg/ml, endothelium removed and intact endothelium aortic rings, respectively). Nevertheless, removal of the endothelium did not significantly change IC50 values when KCl (30 and 80 mM) was used as the contractile agent. The inhibitory effect induced by AFL on high (64.5 mM) K+-induced contraction was potentiated slightly (p < 0.05) by the decrease (from 2.5 to 0.3 mM, Ca2+) and attenuated by the increase (from 2.5 to 7.5 mM Ca2+) in the external [Ca2+]. In addition, in aortas from normotensive rats, AFL antagonized transient contractions induced in Ca2+-free media induced by 1 microM noradrenaline in a concentration-dependent manner, but not those induced by 20 mM caffeine. It is suggested that the remaining vasodilator effect of AFL in normotensive rats is probably due to an inhibition of Ca2+ influx and/or inhibition of intracellular Ca2+ mobilization from the noradrenaline-sensitive stores.

Albizzia↗

PubMed2002

Muscarinic agonist properties involved in the hypotensive and vasorelaxant responses of rotundifolone in rats.

The acute cardiovascular effects of rotundifolone (ROT), the major constituent (63.5 %) of the essential oil of Mentha x villosa (OEMV), were tested in rats by using a combined (in vivo and in vitro) approach. ROT (1, 5, 10, 20 and 30 mg kg(-1) i. v.) induced a significant and dose-dependent hypotension and bradycardia in non-anaesthetized normotensive rats. The hypotensive effect was significantly attenuated by pre-treatment of the rats with atropine (2 mg kg(-1) i. v.) or L-NAME (20 mg kg(-1) i. v.). Furthermore, the bradycardic effect was abolished by atropine. In isolated rat atrial preparations, ROT (10, 100, 300 and 500 microg ml(-1)) produced concentration-related negative inotropic and chronotropic effects. In isolated intact aortic rings, increasing concentractions of ROT (0.3, 1, 10, 100, 300 and 500 microg ml(-1)) were able to antagonize the contractile effect of phenylephrine (1 microM) (IC50 = 184 +/- 6 microg ml(-1)). The smooth muscle-relaxant activity of ROT was inhibited by either removal of vascular endothelium, atropine (1 microM), L-NAME (100 and 300 microM) or indomethacin (10 microM) (IC50 values = 235 +/- 7, 247 +/- 8, 387 +/- 21, 723 +/- 75 and 573 +/- 38 microg ml(-1), respectively). These results suggest that rotundifolone markedly lowers arterial pressure and heart rate in non-anaesthetized animals. The hypotensive action of rotundifolone can be a consequence of a decrease in heart rate and peripheral vascular resistance, probably due to a non-selective muscarinic receptor stimulation.

Animals↗

PubMed2001

CNS pharmacological effects of the total alkaloidal fraction from Albizia inopinata leaves.

The total alkaloidal fraction of Albizia inopinata leaves (FLA) was investigated for its central nervous system (CNS) effects. FLA (10 mg/kg, i.p.) significantly reduced (45%) the locomotor activity in mice. In addition, it inhibited the conditioned avoidance response behavior and induced ptosis in rats. On the other hand, FLA did not exert significant effect on catalepsy, but potentiated the haloperidol-induced catalepsy. No effect was observed on sleep induced by sodium pentobarbital or apomorphine-induced stereotypes.

Animals↗

PubMed2001

Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries.

The hypotensive and vasorelaxant effect of dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively. In intact animals, initial bolus administration of dioclein (2.5 mg kg(-1)) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg(-1)) produced hypotensive responses with no significant change in heart rate. N(G)-nitro-L-arginine methyl ester (L-NAME) did not affect the hypotensive response. In endothelium-containing or -denuded vessels pre-contracted with phenylephrine, dioclein (5 and 10 mg kg(-1) produced a concentration-dependent vasorelaxation (IC(50)=0.3+/-0.06 and 1.6+/-0.6 microM, respectively) which was not changed by 10 microM indomethacin. L-NAME (300 microM) produced a shift to the right. Dioclein was without effect on contraction of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and the concentration dependence of dioclein's effect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl. Tetraethylammonium (10 mM) and BaCl(2) (1 mM) increased the IC(50) for dioclein-induced vasorelaxation without affecting the maximal response (E(max)). Charybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) increased the IC(50) and reduced the E(max). Apamin (1 microM) reduced the E(max) without affecting the IC(50). Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7+/-1.4 mV and 12.3+/-3.6 mV, respectively). In conclusion dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the vasorelaxant effect of dioclein appears to be the opening of K(Ca) and Kv channels and subsequent membrane hyperpolarization.

4-Aminopyridine↗

PubMed2001

Intracellular calcium mobilization as a target for the spasmolytic action of scopoletin.

The coumarin scopoletin was isolated in a pure form from the roots of Brunfelsia hopeana Benth. (Solanaceae). In isolated rat aortic rings, scopoletin (26-520 microM) inhibited to approximately the same extent the contractions induced by a variety of substances, including phenylephrine, potassium chloride, serotonin and PGF(2) (alpha). The effect of the coumarin on phenylephrine-induced contractions was not affected by endothelium removal or NO-synthase blockade by L-NAME (100 microM). Scopoletin (78 - 590 microM) antagonized in a concentration-dependent manner (IC(50) = 300 +/- 20 microM, n = 5), transient contractions in Ca(2+)-free media induced by noradrenaline, but not those induced by caffeine. Also, scopoletin did not interfere with the refilling of noradrenaline-sensitive intracellular calcium stores. It is suggested that the non-specific spasmolytic action of scopoletin can be attributed, at least in part, to its ability to inhibit the intracellular calcium mobilization from the noradrenaline-sensitive stores.

Animals↗

PubMed2000

Mechanisms of the contractile effect of the hydroalcoholic extract of Cissampelos sympodialis Eichl. in the rat aorta.

In the present work the effect of the aqueous fraction of the ethanolic extract of the leaves (AFL) of Cissampelos sympodialis Eichl. was investigated in the rat aorta. In the presence of functional endothelium, AFL produced concentration-dependent contractions (EC50 value of 76.6 +/- 17.8 micrograms/ml). In the absence of functional endothelium, the concentration-response curves to AFL were significantly shifted to the left (EC50 values of 1.3 +/- 0.9 micrograms/ml) without modification of its maximal contractile effect. In the presence of L-NAME (300 microM) and of indomethacin (10 mM), the concentration-response curves produced by AFL were also shifted to the left (EC50 values of 21.8 +/- 6.2 and 24.3 +/- 13.2 micrograms/ml, respectively). The treatment of the aortas with L-NAME (300 microM) plus indomethacin (10 microM) produced a significant shift to the left of the concentration-dependent curves of AFL (EC50 value of 4.9 +/- 2.2 micrograms/ml), similar to that observed in the absence of the vascular endothelium. In addition, AFL-induced contraction was abolished in the presence of prazosin (1 microM), and significantly shifted to the right in the presence of yohimbine (EC50 value of 723.6 +/- 76.4 micrograms/ml). Thus, based on these results, it can be concluded that contractions induced by AFL in the rat aorta were due to activation of alpha-adrenoceptors. Furthermore, these results also showed that the AFL-induced contractions were modulated by the endothelium, via the release of NO and of a cyclooxygenase-derived relaxant product. Finally, it can be concluded that the contractile effects of AFL on vascular smooth muscle may play an important role in the hypertensive effects of this plant in vivo.

Adrenergic alpha-Antagonists↗

PubMed1996

Renin secretion in conscious Lyon hypertensive rats.

To characterize the renin secretory profile in Lyon hypertensive (LH) rats, renin responses to reductions of arterial pressure and beta-adrenoceptor stimulation were assessed in conscious unrestrained LH (n = 13) and Lyon normotensive (LN, n = 14) rats under normal-salt diet. Mean arterial pressure (MAP) in the infrarenal aorta was recorded beat to beat for 3 h. Then, plasma renin concentration (PRC) was measured 1) in basal conditions, 2) during 10-mmHg stepwise reductions of MAP down to 60 mmHg using a chronically implanted aortic inflatable cuff, and 3) during isoprenaline infusion (62.5, 125, and 250 ng.kg-1.min-1 iv). Compared with LN, LH rats had an elevated MAP (146 +/- 3 vs. 111 +/- 1 mmHg, P < 0.001) and decreased PRC [4.2 +/- 0.6 vs. 8.2 +/- 0.8 ng angiotensin (ANG) I.ml-1.h-1, P < 0.001] and kidney renin content (216 +/- 14 vs. 1,149 +/- 103 micrograms ANG I.h-1.g-1, P < 0.001). Pressure-dependent renin release occurred below 90 mmHg in LN rats and below 80 mmHg in LH rats, and its sensitivity in the low-pressure range did not differ between strains. Isoprenaline-induced increases in PRC were weaker (P < 0.01) in LH than in LN rats. In additional LH and LN rats (n = 6-8), acute ANG II AT1-receptor blockade with losartan (20 mg/kg, followed by 10 mg.kg-1.h-1 iv for 2 h) induced lesser (P < 0.001) PRC increases in LH than in LN rats. Renin responses to isoprenaline remained blunted (P < 0.01) during losartan infusion in LH rats. We conclude that, in LH rats, renin secretion is independent of MAP in the range of its spontaneous variations and is poorly responsive to beta-adrenoceptor stimulation, the alteration of which cannot be explained by an enhanced feedback inhibition by ANG II.

Adrenergic beta-Agonists↗

PubMed1994

Pressure-dependent renin release and arterial pressure maintenance in conscious rats.

The relationship between pressure-dependent renin release and mean arterial pressure (MAP) level was assessed in normotensive intact (n = 10), sympathectomized (guanethidine at 1-13 wk of age; n = 8), and renal-denervated (1 wk before the study; n = 6) rats under normal-salt diet. MAP was recorded beat-to-beat for 2 h in conscious animals. Then plasma renin concentration (PRC) responses to graded reductions of MAP were determined using an aortic inflatable cuff. Neither sympathectomy nor renal denervation altered baseline MAP level and PRC. Lowering MAP below a threshold pressure induced large increases in PRC. Threshold pressure did not differ between intact (87 +/- 1 mmHg), sympathectomized (88 +/- 2 mmHg), and renal-denervated (83 +/- 2 mmHg) rats. MAP frequently fell below threshold pressure in sympathectomized but not in intact and renal-denervated rats. We conclude that in conscious normotensive quiet rats under normal-salt diet the pressure-dependent renin release is not activated spontaneously and is therefore unlikely to play a role in MAP maintenance. This regulatory mechanism develops and operates normally in the absence of sympathetic nerves.

Animals↗

PubMed1994

Pressure control of renal renin release in Lyon hypertensive rats.

OBJECTIVE: To assess whether the pressure-independence of renin release by isolated kidneys of Lyon hypertensive (LH) rats could result from long-term exposure to high blood pressure, sodium retention or an altered regulation of intracellular calcium through L-type voltage operated channels. DESIGN: Renin release was studied in kidneys from LH rats, either controls or chronically (aged 3-7 weeks) treated with hydralazine or deprived of sodium. The influence of L-type calcium channels was studied acutely using a specific activator (BAY K8644) or modulator (verapamil). Lyon low blood pressure (LL) rats served as controls. METHODS: Kidneys were isolated from LH or LL rats aged 7 weeks and single-pass perfused at three pressure levels: 70, 85 and 160 mmHg. RESULTS: LH rat kidneys differed from LL rat kidneys in having elevated vascular resistances, decreased glomerular filtration rate, pressure natriuresis and pressure-dependent renin release. Hydralazine treatment and sodium deprivation did not significantly modify the pressure-independence of renin release by LH rat kidneys. BAY K8644 (1 x 10(-8) and 5 x 10(-8) mol/l) induced significantly greater vasoconstrictor effects in LH than in LL rat kidneys but did not affect the renin release already stimulated by low perfusion pressure. Verapamil (5 x 10(-6) mol/l) dilated LH more than LL rat kidneys. It did not change the renin release observed at low, but enhanced it at high, perfusion pressure. This effect was more marked in LL than in LH rat kidneys. CONCLUSIONS: The poor stimulation of renin release by low perfusion pressure in LH rat kidneys does not appear to be a consequence of high blood pressure level, sodium retention and alteration in L-type calcium channels. However, results demonstrate that these channels participate in the increased vascular resistances exhibited by LH rat kidneys.

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

PubMed1993

High blood pressure maintenance in transgenic mRen-2 vs. Lyon genetically hypertensive rats.

The present work was aimed to assess the factors involved in the maintenance of hypertension in adult transgenic mRen-2 (TG) rats. Special attention was paid to the renal handling of sodium, the sympathetic, and the renin-angiotensin system (RAS) activity. TG rats were compared with age-matched Lyon genetically hypertensive rats (LH), as both are of Sprague-Dawley origin. Blood pressure (BP), heart rate, and renal sympathetic nerve activity (RSNA) were recorded in conscious freely moving animals. Kidneys were isolated and single-pass perfused at different pressure levels. It was observed that the peripheral sympathetic drive was identical in TG and LH rats as indicated by their similar 24-h urinary excretion of catecholamines and methoxylated metabolites, baseline RSNA and its control by the baroreflex, and hypotensive response to ganglion-blockade. On the contrary, TG rats differed from LH rats by a more rapid excretion of an oral isotonic sodium load, a greater hypotensive and natriuretic response to furosemide, and a more marked BP response to acute RAS blockade. The TG kidney responses to stepwise changes in renal perfusion pressure (RPP) differed from those of LH rats by significantly higher perfusate flow and glomerular filtration rate. However, the pressure natriuresis curve of TG kidneys did not differ from that of LH rats because of an elevated tubular sodium reabsorption rate. These results suggest that adult TG rats, compared with LH rats, exhibit a tendency toward sodium and water retention, which may explain that despite low renal and circulating renin levels, the RAS remains involved in the maintenance of high BP in that model.

Animals↗

PubMed1992

Pressure independence of renin release by isolated kidneys of Lyon hypertensive rats.

In the present work the influence of perfusion pressure on renal functions and renin release was studied before and after the blockade of thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors using isolated kidneys from 7-week-old genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strain. Kidneys were single pass perfused with Krebs-Henseleit solution with a gelatine derivative (Polygeline) added as an oncotic agent. A servocontrolled system stabilized the renal perfusion pressure (RPP) at any chosen (+/- 1 mm Hg) level. In baseline conditions (RPP, 90 mm Hg), LH (n = 7) kidneys differed from LN (n = 6) and LL (n = 8) controls by increased vascular resistance, decreased glomerular filtration rate, and natriuresis. The LH kidney responses to stepwise changes in RPP (between 60 and 170 mm Hg) differed from those of LN and LL rats by a significantly lower perfusion flow, glomerular filtration rate, and natriuresis. Above all, the reduction in RPP, which induced a marked and highly reproducible renin release in LN and LL kidneys, was devoid of effects in LH kidneys. The blockade of TXA2/PGH2 receptors by AH23848 (4 x 10(-6) M) did not change the baseline (RPP, 90 mm Hg) functions of kidneys of the three strains. During changes in RPP, the responses of LN and LL kidneys were not modified, whereas LH kidneys exhibited significant increases in both glomerular filtration rate and natriuresis. Finally, AH23848 significantly decreased the renin release by kidneys of the three strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Do differences in innervation result in different post-synaptic responses to exogenous agonists?

1. The pharmacological reactivity of the epididymal and prostatic portions of the rat vas deferens to BaCl2, phenylephrine and carbachol were recorded by isometric and isotonic technique. 2. The maximum response induced by the three agonists were similar at the epidiymal end, while at the prostatic portion phenylephrine produced a response 80% lower than that of barium and carbachol. 3. The pD2 value to agonists and the sensitivity to calcium channel blockers were lower at the prostatic end. 4. The data suggest that not only the pharmacological reactivity of the prostatic and epididymal portions differs, but also that the activity of the prostatic portion is much more reduced to alpha 1-agonists.

Animals↗

PubMedDate not supplied

Renin secretion in Lyon hypertensive rats.

In genetically hypertensive rats of Lyon strain (LH), both development and maintenance of hypertension are extremely sensitive to the chronic blockade of the renin-angiotensin system. However, LH rats exhibit a low renin secretory profile as indicated by (1) low basal plasma renin concentration; (2) blunted renin responses to reductions of renal perfusion pressure and beta-adrenoceptor stimulation both in vitro (isolated perfused kidney) and in vivo (conscious rat). None of the latter abnormalities are corrected by chronic sodium deprivation or when hypertension is prevented by hydralazine or perindopril treatment. Future studies will therefore have to elucidate the 'renin paradox' in LH rats.

Adrenergic beta-Agonists↗