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Biomedical subjects

J P Nunes

Publications and source records attributed to J P Nunes.

At least 19 recordsLinked to original sources
PubMed2000

Wall tension and contraction of the aorta in 6-month-old spontaneously hypertensive rats.

1. The present study aimed at comparing the influence of passive tension on the effect exerted by noradrenaline on the thoracic aorta of 6-month-old Wistar and spontaneously hypertensive rats (SHR). 2. Concentration-response curves to noradrenaline were obtained in aorta rings, at two levels of passive tension: 3 and 0.5 g. 3. The maximal responses (in percentage of the maximal response to noradrenaline obtained in the beginning of the experiment at a tension of 2 g) were significantly larger (P < 0.05) at 3 g than at 0.5 g in both kinds of rats: 171 versus 69%, respectively, for SHR; 139 versus 76%, respectively, for Wistar rats. 4. When expressed as mg of active tension per mg of tissue, the maximal contraction at both 3 and 0.5 g was smaller in SHR than in Wistar rats (at 3 g: 64.6 +/- 6.7, n = 6 versus 122.3 +/- 19.1, n = 8, respectively, P < 0.05; at 0.5 g: 24.0 +/- 1.0, n = 6 versus 49.0 +/- 5.9, n = 8, respectively, P < 0.05). 5. Maximal responses to noradrenaline were markedly decreased by cytochalasin B (50 microM) (to 15.2 +/- 6.0%, n = 6, at 3 g and 2.8 +/- 1.9%, n = 6, at 0.5 g in SHR; to 11.8 +/- 2.3%, n = 4, at 3 g and 4.3 +/- 1.3%, n = 4, at 0.5 g in Wistar rats). Cytochalasin B at a lower concentration (4 microM) produced a less marked decrease in responses to noradrenaline in both strains of rats. The presence of cardiovascular structural changes in SHR was confirmed by the fact that the heart weight (mg):body weight (g) was higher in SHR (3.37 +/- 0.06, n = 10) than in Wistar rats (2.40 +/- 0.12, n = 11) (P < 0.05). 6. It is concluded that in 6-month-old SHR the contractile capacity of the aortic tissue is reduced. However, the differential sensitivity of aortic smooth muscle at the two different levels of tension remains present. This difference may depend on filament interaction. Contractions to noradrenaline in the rat aorta are highly dependent on actin polymerization.

Animals↗
PubMed1999

The influence of the wall tension on the contractile responses of arteries.

The present study aimed at determining the influence of tension on the responses of arterial smooth muscle to noradrenaline, phenylephrine and angiotensin II. Concentration-response curves to these agonists were obtained in the rat aorta, at two levels of tension: 3 g (29.4 mN) and 0.5 g (4.9 mN). The results obtained show that the maximal responses to the agonists used (in percent of the maximal response to noradrenaline) were significantly larger (P < 0.05) at 3 g than at 0.5 g: 113% versus 66%, respectively, for noradrenaline; 95% versus 59%, respectively, for phenylephrine; 60% versus 24%, respectively, for angiotensin II. In the presence of gadolinium (100 mumol/L)--a mechanogated ion channel blocker--the responses to noradrenaline at 3 g were still significantly larger than responses at 0.5 g: 103% versus 67%, respectively. The compound H-7 (20 mumol/L)--a protein kinase C inhibitor--caused a marked decrease in the maximal responses to noradrenaline at both levels of tension, the responses being reduced to 44% at 3 g and to 20% at 0.5 g. Isradipine (1 mumol/L)--a calcium channel blocker--caused a slight decrease in the responses to noradrenaline at both levels of tension, the responses being reduced to 86% (3 g) and to 50% (0.5 g). In endothelium-free arterial rings, the responses to noradrenaline at 3 g and 0.5 g were also significantly different: 118% versus 80%, respectively. It is concluded that the tension of the arterial wall is a major factor influencing the effects of vasoconstrictor agents; however the mechanisms underlying this supersensitivity at higher tension remain unknown.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

The role of membrane proximal threonine residues conserved among guanine-nucleotide-binding-protein-coupled receptors in internalization of the m4 muscarinic acetylcholine receptor.

Many guanine-nucleotide-binding-protein-coupled receptors contain consensus sequences for phosphorylation by cAMP-dependent protein kinase (PKA), often located in the membrane proximal regions critically important for receptor signalling. In the present study, we have evaluated by site-directed mutagenesis the role of the putative PKA phosphorylation sites in the m4 muscarinic acetylcholine receptor (mAChR), i.e. Thr145 in the second cytoplasmic loop and Thr399 in the third cytoplasmic loop, and the influence of PKA on m4 mAChR function and internalization. Antagonist binding was unaltered by any of the mutations studied, while the agonist-binding affinity was either not affected (Thr145 alanine), increased (Thr399 alanine) or decreased (Thr399 serine or aspartic acid). m4 mAChR-mediated inhibition of adenylyl cyclase was unaltered by the mutations, except for an approximately tenfold reduced agonist potency of the Thr399 aspartic acid mutated receptor. Agonist-induced receptor internalization was unaltered with Thr399 serine or aspartic acid mutations of the receptors, but was strongly decreased in its rate and extent upon replacement of Thr399, Thr145 or both of these residues with alanine. These mutational effects could not be reproduced by treatment of wild-type receptor-expressing cells with the PKA inhibitor H-8. Furthermore, maximal stimulation of cellular PKA neither affected receptor internalization nor signalling measured as receptor-mediated Ca2+ mobilization. We conclude that the membrane proximal threonine residues of the m4 mAChR are not required for receptor signalling, but replacement by alanine residues can significantly affect receptor internalization, independently of PKA phosphorylation. Sequence comparisons suggest that threonine residues at corresponding positions may be relevant to internalization of other guanine-nucleotide-binding-protein-coupled receptors.

Amino Acid Sequence↗
PubMed1995

Central alpha 2-adrenoceptors and blood pressure regulation in the rat.

The role of alpha 2-adrenoceptors in the central regulation of blood pressure has been questioned, since drugs such as clonidine stimulate both alpha 2-adrenoceptors and imidazoline-preferring receptors. The present work was undertaken to study the influence of alpha 2D-adrenoceptors, encoded by the RG20 gene, on blood pressure in the rat. An antisense phosphodiester oligodeoxynucleotide, directed at nucleotides 4-21 of the RG20 gene, was injected in the right lateral cerebral ventricle, causing an increase in systolic blood pressure, both at 1 and 2 days after the injection, when compared to groups of control rats (injected with the sense oligodeoxynucleotide or a missense oligodeoxynucleotide or distilled water). Antisense oligodeoxynucleotides directed either at nucleotides 65-82 of the RG10 gene (encoding for alpha 2C-adrenoceptors) or at nucleotides 26-43 of the RNG gene (encoding for alpha 2B-adrenoceptors), failed to produce any change in blood pressure after being injected. We conclude that the alpha 2-adrenoceptor encoded by the RG20 gene may play a role in blood pressure regulation in the rat.

Animals↗
PubMed1995

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

OBJECTIVE: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. DESIGN AND METHODS: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring. RESULTS: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. CONCLUSIONS: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

24-hour blood pressure profile early after renal transplantation.

Renal transplant patients are often found to have high blood pressure. We studied 12 cyclosporine-treated patients 8-10 days after kidney transplantation by 24-hour ambulatory blood pressure monitoring, and once again at 35-40 days after kidney transplantation. The patients were found to have high mean blood pressure values at 8-10 days after transplantation, with a significant (p < 0.05) decrease at 35-40 days after transplantation (154.2 +/- 4.9/94.4 +/- 2.8 and 142.2 +/- 4.0/88.6 +/- 2.7 mmHg, respectively). A significant (p < 0.05) decrease in blood pressure values was also noted in the second series of measurements, when compared to the first series, in the day-time systolic and in the night-time systolic and diastolic blood pressure values, but not in the day-time diastolic blood pressure values. An abnormal day/night pattern of blood pressure ("non-dipper") was found in these patients in both occasions, with a difference between average blood pressure values during day- and night-time of 1.3/3.0 (systolic/diastolic) and 5.7/7.6 mm Hg at 8-10 and 35-40 days after transplantation, respectively. This tendency towards attenuation of the "non-dipper" pattern occurred in association with the decrease in body weight and of the dose of immunosuppressive drugs. As hemodynamic factors may play a role in both the short and the long-term function and viability of kidney transplant grafts, the high blood pressure and the "non-dipper" pattern of blood pressure found early after kidney transplantation may require a special therapeutic approach.

Adult↗
PubMed1993

Chloroethylclonidine irreversibly activates postjunctional alpha 2-adrenoceptors in the dog saphenous vein.

This study was aimed at analysing the contractile response of the dog saphenous vein to chloroethylclonidine. At 37 degrees C, chloroethylclonidine (0.1-100 mumol.l-1) caused a long-lasting contraction in both proximal and distal segments of the dog saphenous vein, reaching 77.6 and 52.6% of the maximal response to phenylephrine, respectively. At 18 degrees C, and in both segments, the maximal response to chloroethylclonidine was markedly reduced, whereas that to phenylephrine was not changed and that to UK-14,304 was enhanced. The response to chloroethylclonidine was unaffected by pretreatment with cocaine. Warming to 37 degrees C caused contraction of strips which at 18 degrees C had remained unresponsive to chloroethylclonidine, even if these strips were repeatedly washed before warming. At 18 degrees C, chloroethylclonidine (100 mumol.l-1) did not alter the responses to UK-14,304 and phenylephrine. At 37 degrees C, the contractile response to chloroethylclonidine was antagonized by yohimbine, rauwolscine and prazosin, with the potency rank yohimbine = rauwolscine > prazosin. Phenoxybenzamine (30 nmol.l-1) displaced the concentration-response curve to chloroethylclonidine to the right and depressed its maximum. After phenoxybenzamine, yohimbine continued to be more effective than prazosin, which remained very potent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Severe acute form of adult dermatomyositis treated with cyclosporine.

The classical treatment of severe forms of dermatomyositis includes high doses of steroids and/or cytotoxic agents. Acute forms are frequently life threatening. Because cyclosporine is a fast-acting immunosuppressive drug, it appears to be a good candidate for the treatment of refractory forms of acute dermatomyositis. We report a dramatic improvement of a severe, acute, steroid-resistant adult form after cyclosporine administration. A rapid clinical and biochemical improvement is reported, and the reversibility of immunologic abnormalities is emphasized.

Acute Disease↗
PubMed1991

Alpha 1- and alpha 2-adrenoceptors at different levels of the canine saphenous vein.

Presynaptic alpha2- and postsynaptic alpha1-adrenoceptors were compared at the distal and proximal parts of the dog saphenous vein. The results obtained show that: (1) yohimbine is more effective against postsynaptic responses to phenylephrine distally than proximally. On the contrary, WB-4101 is more effective proximally; (2) phenylephrine increases inositol monophosphate production at both levels, but the increase is more pronounced distally; (3) UK-14, 304 and adrenaline reduce and yohimbine and phentolamine increase the release of 3H-noradrenaline caused by electrical stimulation at both levels. However, while adrenaline as well as the antagonists are equipotent at the two levels, UK-14,304 is more potent distally than proximally. In conclusion, we suggest that: more alpha 1A-adrenoceptors exist distally than proximally; imidazoline sites can exist at the distal level which contribute to the higher potency of UK-14,304 distally.

Animals↗