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R Villalobos-Molina

Publications and source records attributed to R Villalobos-Molina.

At least 19 recordsLinked to original sources
PubMed2006

Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic syndrome.

Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is used in the folk medicine for the treatment of hypertension, diabetes, hepatitis and related diseases. The purpose of the present study was to assess the pharmacological properties of different extracts from Cochlospermum vitifolium bark as potential agent for the treatment of some factors related with metabolic syndrome (MS), a complex disease produced for several pathophysiological factors such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv) extracts were subjected to some pharmacological assays to determine their vasorelaxant and hypoglycemic activity. On the other hand, MECv was also evaluated to determine its hepatoprotective effect on sub-chronic experimental assay. HECv showed a significant endothelium-independent relaxation on rat aorta rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%; denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL, E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg) also showed a significant decrease of blood glucose levels (p<0.05) on normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered to bile duct-obstructed rats to determine its hepatoprotective activity, showing a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT, 45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a crystalline polyphenolic compound from MECv by spontaneous precipitation. Those crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC-MS techniques. Results suggest that Cochlospermum vitifolium could be used as a potential agent against MS since it shows hypoglycemic, vasorelaxant and hepatoprotective properties.

Alanine Transaminase↗
PubMed2006

alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent.

Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.

Animals↗
PubMed2006

Endothelium-independent relaxation of aorta rings by two stilbenoids from the orchids Scaphyglottis livida.

Gigantol (1) and 3,7-dihydroxy-2,4-dimethoxyphenanthrene (2) from the orchid Scaphyglottis livida induced a significant concentration-dependent relaxation of the contractions evoked by noradrenaline (NA) in endothelium-intact and denuded rat aorta rings. Incubation with N(G)-nitro-L-arginine methyl ester (L-NAME, 1x10(-5) M) or methylene blue (MB, 1x10(-7) M) significantly reduced the relaxation induced by the stilbenoids 1 and 2. The results suggested that two or more mechanisms are involved in the vasorelaxant effects of both compounds.

Animals↗
PubMed2006

Captopril therapy decreases both expression and function of alpha-adrenoceptors in pre- hypertensive rat aorta.

1.-- The effects of captopril on alpha(1)-adrenoceptor mRNA and protein and phenylephrine-induced contraction was assessed in aorta of pre-hypertensive spontaneously hypertensive rats. 2.-- Four-week-old SHR and WKY rats were treated with captopril [an angiotensin-converting enzyme (ACE) inhibitor] 3 mg kg(-1) day(-1) for 1 week. 3.-- pA(2) values for BMY 7378, an alpha(1D)-adrenoceptor antagonist, were 8.63-9.20 among the different groups. Schild slopes were close to unity suggesting that contraction was produced primarily by alpha(1D)-adrenoceptor stimulation and was not changed with therapy. 4.-- Alpha(1D)-adrenoceptor mRNA and protein values were higher in pre-hypertensive SHR than in WKY, whereas alpha(1A)-adrenoceptor mRNA was higher in WKY and alpha(1B)-adrenoceptors were similar in both strains, and protein was not significantly different for alpha(1A)- and alpha(1B)-subtypes. 5.-- Captopril decreased maximal contraction in SHR, without having effect in WKY rats, while alpha(1D)-adrenoceptor mRNA was decreased in both rat strains but alpha(1D)-adrenoceptor protein was significantly decreased only in SHR, and increased alpha(1A)-mRNA in SHR, no effect of captopril treatment was observed on alpha(1B)-adrenoceptor mRNA and protein nor on alpha(1A)-adrenoceptor protein. 6.-- These data suggest that ACE inhibition by captopril influences both expression and function of alpha(1D)-adrenoceptors in aorta of pre-hypertensive rats, probably avoiding alpha(1D)-subtype expression by blockade of angiotensin II synthesis.

Adrenergic alpha-Agonists↗
PubMed2006

Selective agonists reveal alpha(1A)- and alpha(1B)-adrenoceptor subtypes in caudal artery of the young rat.

Multiple alpha(1)-adrenoceptors were evaluated in caudal artery of the young Wistar rat using selective agonists and antagonists. Arteries were exposed to the selective alpha(1A)-adrenoceptor agonist, A-61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) or to phenylephrine and to prazosin (alpha(1)-adrenoceptor antagonist), or the selective alpha(1A)-adrenoceptor antagonists 5-methylurapidil, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H)-pyrimidinedione), RS 17053 (N-[2(2-cyclopropylmethoxy) ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamide), and the selective alpha(1D)-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione). Results showed a 100-fold higher potency of A-61603 for the alpha(1)-adrenoceptor present in the artery, compared with phenylephrine. Prazosin displaced both agonists with high affinity, whereas 5-methylurapidil, RS 100329 and RS 17053 displaced A-61603 with high affinity, indicating the presence of alpha(1A)-adrenoceptors. The selective alpha(1A)-adrenoceptor antagonists blocked phenylephrine responses with low affinity, suggesting that phenylephrine activated a second receptor population in caudal artery. BMY 7378 antagonized with low affinity both A-61603 and phenylephrine-induced contractions, indicating absence of alpha(1D)-adrenoceptors in the vessel. The results suggest that functional alpha(1B)-adrenoceptors are present in caudal arteries of the young Wistar rat.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2005

Functional characterization of brain mitochondrial nitric oxide synthase during hypertension and aging.

Nitric oxide (NO*) plays an important role in various physiological processes. The aim of the present study was to investigate if brain mitochondrial nitric oxide synthase (mtNOS) is active and functional during hypertension. L-citrulline production, an indicator of nitric oxide synthesis, was concentration-dependent on L-arginine in all strains and all ages tested, and was inhibited by 7-Nitroindazole (7-NI). Brain mitochondria of 1 month-old (prehypertensive) spontaneously hypertensive rats (SHR) exhibited a significantly (p < 0.05) low basal L-citrulline content as compared to age-matched Wistar (W) and Wistar-Kyoto (WKY) rats. L-citrulline synthesis in SHR rats showed a significant (p < 0.01) low response to L-arginine in 3 and 7 months-old rats. Respiratory rates in states 3 and 4 increased with low L-arginine concentration in all strains and all ages. The results suggest that in rat brain mitochondria, L-citrulline synthesis is constant once age-related hypertension is installed and NO* does not regulate oxidative phosphorylation.

Aging↗
PubMed2005

Postjunctional alpha1-adrenoceptors in the vasculature of the pithed mouse are of the alpha1A-subtype.

1. The pressor action of noradrenaline and its blockade by selective alpha(1)-adrenoceptor antagonists in the pithed mouse were evaluated. 2. Chloroethylclonidine (alpha(1B/D)-adrenoceptor alkylating agent) or BMY 7378 (alpha(1D)-adrenoceptor antagonist), both at 1 mg kg(-1), did not block the increase in blood pressure induced by noradrenaline. 3. 5-Methylurapidil (alpha(1A)-adrenoceptor antagonist), at 0.1 mg kg(-1), displaced the dose-response curve approximately six-fold to the right. 4. The results support the idea that the pithed mouse vasculature express alpha(1A)-adrenoceptors and suggest that it is a good model to study the roles of alpha(1)-adrenoceptors in gene knockout or overexpression.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

Chloroethylclonidine reveals that alpha (1 A)-adrenoceptors mediate contraction in aorta of alpha (1 D)-adrenoceptor knockout mice.

1 We have characterized the alpha(1)-adrenoceptor subtypes present in isolated aorta of the alpha(1D)-adrenoceptor knockout (KO) mice, by chloroethylclonidine (CEC)-induced alkylation and their protection by selective alpha(1)-adrenoceptor antagonists. 2 The alpha(1D)-adrenoceptor is involved in the contractile response to noradrenaline in wild type (WT) mouse aorta. 3 In WT mice 5-methylurapidil (5-MU, an alpha(1A)-adrenoceptor antagonist) or BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9 dione, a selective alpha(1D)-adrenoceptor antagonist), protected the receptors from CEC-induced (alpha(1B/D)-adrenoceptor) alkylation, the combination of both antagonists resulted in complete protection, while AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol, an alpha(1B)-adrenoceptor antagonist) did not protect. 4 In aorta of KO mice there was a 19-fold rightward shift in noradrenaline effective concentration (EC(50)) compared with WT; while 5-MU alone or in combination with AH11110A protected alpha(1)-adrenoceptors to the same extent. 5 The data indicate that alpha(1A)-adrenoceptors mediate contraction and suggest their role in maintaining homeostasis in the alpha(1D)-adrenoceptors KO mice.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

WAY 405, a new silent 5-HT (1A) receptor antagonist with low affinity for vascular alpha (1)-adrenoceptors.

1 The effect of WAY 405 ((R)-N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide), a putative 5-HT(1A) receptor antagonist, on cardiovascular function was studied. 2 In anaesthetized rats, the i.v. injection of WAY 405 did not significantly modify basal heart rate nor blood pressure at doses of 1, 3, 10 and 30 microg kg(-1); while the antagonist dose dependently antagonized the 5-HT(1A) receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced hypotension and bradycardia. 3 WAY 405 antagonized noradrenaline-induced contraction in isolated arteries, with pK(B) values of 6.6+/-0.1, 6.5+/-0.1 and 6.5+/-0.1, for rat tail artery (alpha(1A)-adrenoceptors), rabbit aorta (alpha(1B)-adrenoceptors), and rat aorta (alpha(1D)-adrenoceptors) respectively. 4 The results show that in the control of blood pressure the new compound, WAY 405, behaves as a silent 5-HT(1A) receptor antagonist in the anaesthetized rat, also having low affinity for vascular alpha(1)-adrenoceptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2004

Spasmolytic stilbenoids from Maxillaria densa.

2,5-dihydroxy-3,4-dimethoxyphenanthrene (1), fimbriol-A (2), nudol (3), gymnopusin (4) and erianthridin (5) isolated from Maxillaria densa provoked a concentration-dependent inhibition of the spontaneous contractions of the rat ileum with potencies comparable to papaverine. In order to establish the mode of action of stilbenoids 1-5, their effect on the contractions induced by different spasmogens (histamine, barium chloride and L-NAME) was investigated. In general, the results suggested that the relaxant activity of the products does not involve a direct nitrergic or antihistaminergic mode of action or an interference with calcium influx into the smooth muscle cells.

Animals↗
PubMed2002

Regulation of the rate of synthesis of nitric oxide by Mg(2+) and hypoxia. Studies in rat heart mitochondria.

In isolated rat heart mitochondria, L-arginine is oxidized by a nitric oxide synthase (mtNOS) achieving maximal rates at 1 mM L-arginine. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (NAME) inhibits the increase in NO production. Extramitochondrial free magnesium inhibited NOS production by 59% at 3.2 mM. The mitochondrial free Mg(2+) concentration increased to different extents in the presence of L-arginine (29%), the NO donor (S-nitroso-N-acetylpenicillamine) (105%) or the NOS inhibitors L-NAME (48%) or N(G)-nitro-L-arginine methyl ester, N(G)-monomethyl-L-arginine (L-NMMA) (53%). Under hypoxic conditions, mtNOS activity was inhibited by Mg(2+) by up to 50% after 30 min of incubation. Reoxygenation restored the activity of the mtNOS to pre-hypoxia levels. The results suggest that in heart mitochondria there is an interaction between Mg(2+) levels and mtNOS activity which in turn is modified by hypoxia and reoxygenation.

Animals↗
PubMed2002

Evidence that the hypotensive effect of WAY 100635, a 5-HT1A receptor antagonist, is related to vascular alpha 1-adrenoceptor blockade in the adult rat.

1. The effect of WAY100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), a 5-HT1A receptor antagonist, on cardiovascular function was studied. 2. The i.v. injection of WAY100635 dose-dependently decreased blood pressure in anaesthetized rats; while in pithed rats WAY100635 (1 mg kg(-1)) displaced the phenylephrine pressor effect. 3. WAY100635 antagonized phenylephrine-induced contraction in rabbit and rat aorta (pA2 of 6.88 and 7.93 and Schild slopes of -0.83 and -1.21, respectively); while in rat caudal artery pK(B) was 7.45 and the Schild slope of -0.56, suggesting a complex interaction in this vessel. 4. The results show that WAY100635 induced hypotension in the anaesthetized rat and suggest that this effect could be partially explained by antagonism of vascular alpha1-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Effects of chronic morphine and N(6)-cyclopentyl-adenosine administration on kainic acid-induced status epilepticus.

The aim of the present study was to investigate if the upregulation of mu or A(1) receptors modifies the expression of the kainic acid (KA)-induced status epilepticus (SE). Male Wistar rats received one of the following treatments: saline solution (SS) (1 ml/kg, i.p. for 7 days); morphine (M) (20 mg/kg, i.p. for 7 days) or N(6)-cyclopentyl-adenosine (CPA) (1 mg/kg, i.p. for 9 days). Twenty-four hours after the last administration rats were sacrificed. Membranes were obtained mu and and A(1) receptor binding experiments were carried out. Furthermore, an injection of SS (1 ml/kg, i.p.) or KA (10 mg/kg, i.p.) was applied in rats pretreated chronically with M, CPA or SS, 48 h after the last administration. Seizure activity, death rate and a postictal explosive motor behavior were evaluated after KA administration. Chronic M administration increased mu receptor number in hippocampus (115%) and cortex (265%), whereas chronic CPA treatment enhanced A(1) receptor number in hippocampus (55%), amygdala (39%) and cortex (51%). The pretreatment with M facilitated the KA-induced SE and reduced the death rate as well as the postictal explosive motor behavior. The pretreatment with CPA delayed the SE presentation, increased the death rate and decreased the postictal explosive motor behavior. These findings suggest that upregulation of mu receptors enhances the KA seizures, whereas upregulation of A(1) receptors depresses these seizures.

Adenosine↗
PubMed2000

Differential response to chloroethylclonidine in blood vessels of normotensive and spontaneously hypertensive rats: role of alpha 1D- and alpha 1A-adrenoceptors in contraction.

The effects of chloroethylclonidine on alpha(1)-adrenoceptor-mediated contraction in endothelium-denuded caudal arteries and aorta from normotensive Wistar and Wistar Kyoto (WKY), and from spontaneously hypertensive (SHR) rats were evaluated. Chloroethylclonidine elicited concentration-dependent contractions. Maximal contraction was similar in caudal arteries among strains ( approximately 40% of noradrenaline effect). However, chloroethylclonidine elicited a higher contraction in aorta from SHR than from normotensive rats. In Wistar aorta chloroethylclonidine produced the smallest contractile response. In SHR aorta, BMY 7378 and 5-methylurapidil blocked chloroethylclonidine-elicited contraction, while (+)-cyclazocine did not inhibit it; while in caudal arteries, 5-methylurapidil blocked chloroethylclonidine action; the other antagonists had no effect. In chloroethylclonidine-treated aorta noradrenaline elicited biphasic contraction-response curves, indicating a high affinity (pD(2), 8.5 - 7.5) chloroethylclonidine-sensitive component and a low affinity (pD(2), 6.3 - 5.2) chloroethylclonidine-insensitive component. The high affinity component was blocked by chloroethylclonidine; while in caudal arteries noradrenaline elicited monophasic contraction-response curves with pD(2) values (6.5 - 5.7) similar to the low affinity component in aorta. Chloroethylclonidine inhibition of noradrenaline response was greater in aorta than in caudal arteries. Chloroethylclonidine increased the EC(50) values of noradrenaline approximately 1000 fold in aorta and approximately 10 fold in caudal arteries. In SHR aorta BMY 7378 protected alpha(1D)-adrenoceptors and in caudal arteries 5-methylurapidil protected alpha(1A)-adrenoceptors from chloroethylclonidine alkylation, allowing noradrenaline to elicit contraction. These results show marked strain-dependent differences in the ability of chloroethylclonidine to contract aorta; moreover, chloroethylclonidine stimulates alpha(1D)-adrenoceptors in aorta and alpha(1A)-adrenoceptors in caudal arteries. The higher contraction observed in aorta from SHR and WKY suggests an augmented number of alpha(1D)-adrenoceptors in these strains.

Adrenergic alpha-Antagonists↗
PubMed2000

The alpha-adrenoceptor antagonist, zolertine, inhibits alpha1D- and alpha1A-adrenoceptor-mediated vasoconstriction in vitro.

1. The antagonist effect of zolertine (4-phenyl-1-[2-(5-tetrazolyl)ethyl]piperazine trihydrochloride), on vascular contraction elicited by noradrenaline in aorta, carotid (alpha1D-adrenoceptors), mesenteric (alpha1A/D-adrenoceptors) and caudal arteries (alpha1A-adrenoceptors) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats and rabbit aorta (alpha1B-adrenoceptors), was investigated in endothelium-denuded arterial rings. 2. The selective alpha1D-adrenoceptor agonist, noradrenaline, elicited concentration-dependent contractions in all arterial rings from both species. Noradrenaline selectivity was: carotid = aorta >> mesenteric = rabbit aorta > caudal arteries. 3. The contractile responses induced by noradrenaline were competitively antagonized by zolertine in rat carotid and aorta arteries, yielding pA2 values of WKY, 7.48 +/- 0.18; SHR, 7.43 +/- 0.13 and WKY, 7.57 +/- 0.24; SHR, 7.40 +/- 0.08, respectively. Zolertine was a non-competitive antagonist in some blood vessels as Schild plot slopes were lower than unity. The pKb estimates for zolertine were WKY, 6.98 +/- 0.16; SHR, 6.81 +/- 0.18 in the mesenteric artery, WKY, 5.73 +/- 0.11; SHR, 5.87 +/- 0.25 in the caudal artery and 6.65 +/- 0.09 in rabbit aorta. 4. Competition binding experiments using the alpha1-adrenoceptor antagonist [3H]prazosin showed a zolertine pKi of 6.81 +/- 0.02 in rat liver (alpha1B-adrenoceptors) and 6.35 +/- 0.04 in rabbit liver (alpha1A-adrenoceptors) membranes. 5. Zolertine showed higher affinity for alpha1D-adrenoceptors compared to alpha1A-adrenoceptors, while it had an intermediate affinity for alpha1B-adrenoceptors. The ability of the alpha1-adrenoceptor antagonist zolertine to block alpha1D-adrenoceptor-mediated constriction in different vessels of WKY and SHR rats may explain its antihypertensive efficacy despite its low order of potency.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

Functional evidence of alpha1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats.

The role of alpha1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of alpha1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure.

Aging↗
PubMed1998

Chloroethylclonidine is a partial alpha1-adrenoceptor agonist in aorta and caudal arteries of the Wistar Kyoto rat.

The interaction between chloroethylclonidine (N-beta-chloroethyl-N-methylamino-methyl-clonidine) and alpha1-adrenoceptors mediating contraction in Wistar Kyoto rat arteries was examined. In caudal (alpha1A-adrenoceptors) and aorta (alpha1D-adrenoceptors) arteries, chloroethylclonidine (10(-4) M) elicited contraction with different time frames (maximal effect within 4 min in the caudal artery and at 30-45 min in aorta). Phentolamine (10(-6) M) completely prevented chloroethylclonidine-induced contraction in aorta, but partially did so in the caudal artery. Rauwolscine (10(-7) M) partially prevented the chloroethylclonidine contractile effect in both arteries. Chloroethylclonidine attenuated the contractile effect of low concentrations of norepinephrine, however, maximal contraction was observed at catecholamine concentrations above 10(-7) M in the caudal artery and 10(-6) M in the aorta. It is concluded that chloroethylclonidine interacts with caudal alpha1A-adrenoceptors as an irreversible partial agonist, inducing vascular contraction probably due to Ca2+ mobilisation, and with aorta alpha1D-adrenoceptors as a partial agonist, inducing slow-onset muscular contraction.

Adrenergic alpha-1 Receptor Agonists↗