Biomedical subjects

R Villalobos-Molina

Publications and source records attributed to R Villalobos-Molina.

62 records · Page 4Linked to original sources

PubMedDate not supplied

Oxidative stress and age-related neuronal deficits.

Research from our laboratory has indicated that the loss of sensitivity that occurs in several receptor systems as a function of age may be an index of an increasing inability to respond to oxidative stress (OS). This loss occurs partially as a result of altered signal transduction (ST). Assessments have involved determining the nature of age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model, we have found that 1. Reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from striatal slices from both young and old animals could be restored with alpha-tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be induced with radiation exposure; and 4. Pre-incubation of the striatal slices with cholesterol decreased subsequent deleterious effects of NO or OH. on DA release. Thus, cholesterol, which increases in neuronal membranes as a function of age, may function as a potent antioxidant and protectant against neuronal damage. These results suggest that therapeutic efforts to restore cognitive deficits in aging and age-related disease might begin with antioxidant reversal of ST decrements.

Aging↗

PubMedDate not supplied

Effects of moderate chronic ethanol consumption on rat liver mitochondrial functions.

The biochemical consequences of moderate chronic ethanol ingestion has been scarcely investigated in spite of the fact that most of the human population drinks ethanol on a moderate basis. This paper describes some metabolic effects produced by moderate ethanol consumption. The substitution of drinking water in rats for a 10% ethanol solution during 4 weeks resulted in: a) a decrease of blood urea and citrulline synthesis in liver mitochondria; b) a slight inhibition in state 3 and state 4 respiration either with glutamate-malate as substrates or succinate as substrate; c) no change in ADP/O ratio with succinate but slight increase with glutamate-malate; d) a reduction of the cytochrome oxidase activity and cytochromes a+a3 content; e) a 42% increase in the succinate dehydrogenase activity and a small but constant increase in the Vmax (no change in the Km) of the adenine nucleotide translocase activity in liver mitochondria. These results show that even moderate, but continuous ethanol ingestion, produces metabolic responses that must be carefully evaluated to define health risk in larger human groups.

Adenosine Diphosphate↗

PubMedDate not supplied

Patterns of adrenoceptor change during liver regeneration of the Wistar Kyoto rat: a binding study.

BACKGROUND: Adrenoceptors have been involved in the regulation of hepatocyte proliferation after partial hepatectomy, as well as in primary culture. This report characterizes alpha 1- and beta-adrenoceptor change during the time-course of liver regeneration in adult Wistar Kyoto rats. METHODS: Saturation binding assays with [3H]prazosin or [3H]dihydroalprenolol (for alpha 1- and beta-adrenoceptors, respectively) were done in liver plasma membranes from 6-month-old rats subjected to 70% hepatectomy followed by hepatic regeneration. RESULTS: [3H]Prazosin and [3H]dihydroalprenolol binding gave control Bmax values of 101 +/- 10 and 12 +/- 1 fmol/mg protein and Kd of 0.50 +/- 0.10 and 4.1 +/- 0.4 nM for alpha 1- and beta-adrenoceptors, respectively. alpha 1-Adrenoceptor number and Kd increased at 24 and 48 h and returned to control values at 72 and 96 h after surgery, whereas beta-adrenoceptors augmented at 48 and 72 h, with a Kd change at 24 and 48 h posthepatectomy. CONCLUSIONS: These results suggest that dual control of alpha 1- and beta-adrenoceptor membrane expression could be involved in different steps during hepatocyte proliferation, and that Wistar Kyoto rats have a different adrenoceptor pattern expression from other rat strains.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Vascular alpha 1D-adrenoceptor function is maintained during congestive heart failure after myocardial infarction in the rat.

BACKGROUND: During congestive heart failure, desensitization of beta-adrenoceptors is related to a lower adrenergic responsiveness in the heart; little is known about alpha 1-adrenoceptors in the vasculature under this condition. We evaluated alpha 1D-adrenoceptor response in aorta and carotid arteries in a model of congestive heart failure (CHF) post-myocardial infarction. METHODS: Noradrenaline-elicited contraction was determined in endothelium-denuded arterial rings from young (10-week-old) Wistar rats in the absence and presence of the alpha 1D-adrenoceptor antagonist BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-8-azaspiro(4,5)decane-7,9-dione dihydrochloride) in sham-operated rats and in rats that developed CHF 4 weeks or 7 months after myocardial infarction. RESULTS: In the thoracic aorta, BMY 7378 displaced noradrenaline effect to the right with pA2 values of: sham, 8.58 +/- 0.12; CHF, 8.36 +/- 0.13, and sham, 8.56 +/- 0.10; CHF, 7.99 +/- 0.13 at 4 weeks and 7 months after myocardial infarction, respectively. While in carotid arteries, the pA2 values were: sham, 8.43 +/- 0.19; CHF, 8.81 +/- 0.19, and sham, 8.35 +/- 0.18; CHF, 8.29 +/- 0.08 at 4 weeks and 7 months after myocardial infarction, respectively. When adult (7-month-old) rats were subjected to myocardial infarction, CHF was not installed and pA2 values were similar and high in both sham and infarcted rats. CONCLUSIONS: These results indicate that alpha 1D-adrenoceptors remained as the main receptors involved in contraction in aorta and carotid arteries, irrespective of CHF duration.

Adrenergic alpha-1 Receptor Antagonists↗

PubMedDate not supplied

Vascular alpha 1D-adrenoceptors: are they related to hypertension?

Heterogeneity of vascular alpha 1-adrenoceptor subtypes has been revealed by pharmacological and molecular biology studies (i.e., alpha 1A-, alpha 1B-, and alpha 1D-adrenoceptors). The alpha 1D-adrenoceptor subtype is predominantly involved in the contraction of a variety of vessels and its role in the control of blood pressure has been suggested, a phenomenon probably related to aging. Recent advances in the use of young pre-hypertensive rats and adult spontaneously hypertensive rats with one kidney and Grollman-type renal hypertension suggest vascular alpha 1D-adrenoceptor involvement in the increased blood pressure. The possible role of alpha 1D-adrenoceptors in the genesis/maintenance of hypertension is discussed in this review.

Animals↗

PubMedDate not supplied

Alpha 1-adrenoceptors: subtypes, signaling, and roles in health and disease.

Alpha 1-adrenoceptors mediate some of the main actions of the natural catecholamines, adrenaline, and noradrenaline. They participate in many essential physiological processes, such as sympathetic neurotransmission, modulation of hepatic metabolism, control of vascular tone, cardiac contraction, and the regulation of smooth muscle activity in the genitourinary system. It is now clear that alpha 1-adrenoceptors mediate, in addition to immediate effects, longer term actions of catecholamines such as cell growth and proliferation. In fact, adrenoceptor genes can be considered as protooncogenes. Over the past years, considerable progress has been achieved in the molecular characterization of different alpha 1-adrenoceptor subtypes. Three main subtypes have been characterized pharmacologically and in molecular terms. Splice variants, truncated isoforms, and polymorphisms have also been detected. Similarly, it is now clear that these receptors are coupled to several classes of G proteins that, therefore, are capable of modulating different signaling pathways. In the present article, some of these aspects are reviewed, together with the distribution of the subtypes in different tissues and some of the known roles of these receptors in health and disease.

Amino Acid Sequence↗

PubMedDate not supplied

The influence of chloroethylclonidine-induced contraction in isolated arteries of Wistar Kyoto rats: alpha1D- and alpha1A-adrenoceptors, protein kinase C, and calcium influx.

BACKGROUND: It has recently been reported that chloroethylclonidine (CEC) elicited contraction in tail arteries (alpha(1A)-adrenoceptors) and aorta (alpha(1D)-adrenoceptors) from normotensive and spontaneously hypertensive rats (SHR). This study investigated the relationship between CEC-induced contraction and the role of protein kinase C (PKC) and extracellular Ca(++) influx in tail arteries and aorta from Wistar Kyoto rats (WKY). METHODS: Time-course of CEC-induced contraction in endothelium-denuded arteries from Wistar, WKY, and SHR rats was evaluated. In WKY arteries, calphostin C (1 x 10(-6) M) and nitrendipine (1 x 10(-6) M) were used to determine the role of PKC and extracellular Ca(+1) in the contractile response to CEC, respectively. RESULTS: Chloroethylclonidine (1 x 10(-4) M) elicited contraction in tail arteries and aorta from normotensive and hypertensive rats. Maximal response to CEC was similar in tail arteries among strains (approximately 30% of norepinephrine effect), while in aorta CEC elicited a higher contraction in WKY and SHR than in Wistar (59, 86, and 18% of norepinephrine effect, respectively). CEC-elicited maximal contractile responses were reached in 5 min in tail arteries and in 30-45 min in aorta irrespective of the rat strain, suggesting that different intracellular signaling pathways are involved in the contractile response to CEC in these arteries. In WKY tail arteries, calphostin C and nitrendipine blocked CEC-induced contraction while in aorta nitrendipine, but not calphostin C, inhibited CEC action. CONCLUSIONS: This study confirms marked strain-dependent differences in rat aorta responsiveness to CEC and suggests a central role for PKC in response to CEC in tail arteries and for extracellular Ca(+1) influx in aorta.

Acetylcholine↗

PubMedDate not supplied

The hypotensive effect of BMY 7378 is antagonized by a silent 5-HT(1A) receptor antagonist: comparison with 8-hydroxy-dipropylamino tetralin.

BACKGROUND: Stimulation of central 5-HT(1A) receptors produces bradycardia and diminishes blood pressure in conscious or anesthetized rats. Our objective was to investigate the effects on blood pressure and heart rate of the partial 5-HT(1A) receptor agonist and selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro [4.5] decane-7,9 dione hydrochloride) compared to the full 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-dipropylamino tetralin) in adult anesthetized rats. METHODS: Male Wistar rats of 6 months of age were exposed intravenously (i.v.) to increasing doses of BMY 7378 or 8-OH-DPAT in the absence and presence of WAY 100635. Blood pressure and heart rate were continuously recorded. RESULTS: BMY 7378 induced a decrease in blood pressure with no apparent change in heart rate compared to basal values, while 8-OH-DPAT decreased both hemodynamic parameters. BMY 7378 hypotensive effect was antagonized by the selective, silent 5-HT(1A) receptor antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). However, a remnant yet significant hypotensive effect was not blocked by the antagonist. In contrast, 8-OH-DPAT actions were completely blocked by WAY 100635. CONCLUSIONS: Data suggest that BMY 7378 cardiovascular effects are related to activation, as a full agonist, of central 5-HT(1A) receptors in adult rats; however, participation of other systems such as vascular alpha1-adrenoceptors in cardiovascular function is suggested.

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