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M Ibarra

Publications and source records attributed to M Ibarra.

At least 19 recordsLinked to original sources
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

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↗
PubMed2004

The cost of medical care and people's health-seeking behaviour before being suspected of tuberculosis in three local health systems, Nicaragua.

OBJECTIVE: To assess the medical costs incurred by users and delay between first contact with a care provider and sputum test for acid-fast bacilli (AFB) in three areas of Nicaragua. METHODS: Directed interviews of consecutive series of tuberculosis (TB) suspects whose sputum had been examined for AFB. RESULTS: Of 252 TB suspects interviewed, 52% used more than one type of care giver and 35% used private practitioners. As a consequence, 18%, 21% and 29% of the interviewees in Carazo, El Viejo and Matagalpa, respectively, spent more than 1 month of the country's median income per inhabitant on medical care between the first visit to a care provider and the first sputum examination. Furthermore, more than 3 months elapsed on that part of the care pathway for 30%, 17% and 3% of interviewees in Matagalpa, El Viejo and Carazo, respectively. CONCLUSION: This study sheds light on the costs and delays incurred by TB suspects before reaching a laboratory for sputum smear examination. Both costs are lower for those suspects who exclusively use first-line governmental health services (FLGHS). This has been relatively little documented in Latin America to date and could be used as an argument to develop strategies to strengthen the credibility of FLGHS.

Bacteriological Techniques↗
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

Reconstruction with rectus abdominis myocutaneous free flap after orbital exenteration in children.

OBJECTIVE: To present a 1-stage technique for orbital reconstruction after exenteration with the use of myocutaneous rectus abdominis free flap in children. SURGICAL TECHNIQUE: After orbital exenteration, a myocutaneous rectus abdominis free flap with long vascular pedicle is harvested from the abdomen. The flap is transferred to the orbit and the vascular pedicle is passed through an opening made in the lateral orbital wall, where it is anastomosed to superficial temporal vessels. The skin of the flap is trimmed to correspond to the eyelid defect and the incisions are closed. METHODS: After informed consent was obtained, 2 children, 3 and 8 years old, underwent orbital reconstruction with a rectus abdominis free flap after exenteration for orbital rhabdomyosarcoma and orbital osteosarcoma in the setting of retinoblastoma. RESULTS: This technique allowed easy postoperative wound care. Viability of the flap was excellent. The technique provided sufficient volume to fill the orbit, with improved aesthetic results and minimal donor site deformity. CONCLUSIONS: The postoperative care and aesthetic outcome in patients with rectus abdominis free flap after exenteration are much improved over those provided with traditional surgical techniques. This primary reconstruction is recommended for any patient requiring orbital exenteration, but particularly for pediatric patients who tolerate debridement of traditional exenteration sites poorly.

Child↗
PubMed2001

Mechanisms involved in SNP-induced relaxation and [Ca+]i reduction in piglet pulmonary and systemic arteries.

1. We have compared the mechanisms involved in sodium nitroprusside (SNP)-induced relaxation and [Ca2+]i reduction in isolated piglet pulmonary (PA) and mesenteric (MA) arteries. 2. SNP (10(-8) M-3x10(-5) M) evoked a concentration-dependent relaxation of PA and MA (pD2=6.66+/-0.06 and 6.74+/-0.14, respectively) stimulated by noradrenaline, which was markedly reduced by the guanylate cyclase inhibitor ODQ. In fura 2-incubated PA and MA, SNP produced a parallel reduction in contractile force and in [Ca2+]i, expressed as the ratio of emitted fluorescence at 340 and 380 nm (F340/F380). 3. The inhibition of the Na+/K+-ATPase after the incubation in a K+-free medium or the exposure to ouabain (10(-6) M) inhibited SNP-induced relaxation in MA but not in PA. SNP-induced relaxation was not attenuated by 80 mM KCl plus nifedipine (10(-6) M) but was inhibited by thapsigargin (2x10(-6) M; pD2=5.69+/-0.19 and 5.89+/-0.19 for PA and MA, respectively). 4. Pretreatment of PA with thapsigargin and MA with thapsigargin plus ouabain induced a stronger inhibition on the reduction in [Ca2+]i than on the relaxation induced by SNP, indicating the existence of Ca2+-independent mechanisms. 5. The activation of the Na+/K+-ATPase by the addition of KCl after the incubation in a K+-free medium similarly reduced [Ca2+]i in PA and MA, whereas it relaxed with much less efficacy PA than MA. 6. We conclude that SNP reduces [Ca2+]i and causes relaxation through the activation of SERCA in PA and SERCA and Na+/K+-ATPase in MA. However, Ca2+-independent mechanisms also contribute to SNP-induced effects.

Animals↗
PubMed2001

Nitric oxide- and nitric oxide donors-induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries.

Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP) were analysed in isolated endothelium-denuded pulmonary arteries from 2-week-old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC(30)=7.73+/-0.12, 7.26+/-0.17 and 6.43+/-0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10(-6) M) or the sarcoplasmic Ca(2+)-ATPase thapsigargin (2x10(-6) M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3x10(-7) M) or diethyldithiocarbamate (1 mM) markedly inhibited NO- (pIC(30)=6.88+/-0.07 and 6.92+/-0.18, respectively), weakly inhibited SNAP- and had no effect on SNP-induced relaxation. Xanthine oxidase (5 mu ml(-1)) plus hypoxanthine (10(-4) M) markedly inhibited NO- (pIC(30)=6.96+/-0.12) but not SNAP- or SNP-induced relaxation. Superoxide dismutase (SOD), MnCl(2), diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC(30)=8.52+/-0.16, 8.23+/-0.11, 8.01+/-0.11 and 8.20+/-0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP- or SNP-induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide.

Animals↗
PubMed2001

Pulmonary artery vasoconstriction but not [Ca2+]i signal stimulated by thromboxane A2 is partially resistant to NO.

To characterize the thromboxane A2 (TXA2) -induced resistance to the vasodilator effects of the nitric oxide (NO)/cGMP pathway in pulmonary arteries, we have studied the effects of the NO donor sodium nitroprusside on intracellular calcium concentration ([Ca2+]i) and contractile force recorded simultaneously in isolated piglet pulmonary arteries loaded with fura-2 and contracted with norepinephrine or the TXA2 mimetic U46619 and by activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate. In the TXA2 mimetic- and phorbol 12-myristate 13-acetate plus norepinephrine-stimulated arteries, nitroprusside exhibited lower vasodilator efficacy (and lower potency in the TXA2 mimetic-stimulated arteries) but similar reductions in [Ca2+]i compared with arteries activated by norepinephrine. The nonselective serine/threonine kinase inhibitor staurosporine, but not the selective inhibitor of PKC bisindolylmaleimide, potentiated the relaxation of nitroprusside in the TXA2 mimetic-stimulated arteries. In conclusion, the resistance to NO/cGMP-induced vasodilation in arteries stimulated by TXA2 and PKC involves a reduced ability of the Ca2+-independent mechanisms for smooth muscle vasodilation. The resistance to NO in arteries stimulated by TXA2 is sensitive to staurosporine but not to bisindolylmaleimide, suggesting the involvement of an activation of a serine/threonine kinase distinct from PKC.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Propafenone modulates potassium channel activities of vascular smooth muscle from rat portal veins.

We have studied the effects of the class Ic antiarrhythmic propafenone on K+ currents in freshly isolated smooth muscle cells from rat portal veins and on the spontaneous contractions in whole tissues. Under Ca2+-free conditions, when cells were clamped at -80 mV (whole-cell configuration) depolarizing steps from -80 to +50 mV induced a family of K+ currents (I(Ktotal)) that mainly comprised the delayed rectifier current [I(K(V))], whereas when held at -10 mV only small-amplitude, noninactivating, currents (I(NI)) were recorded. Propafenone (10 microM) markedly inhibited I(Ktotal), but at potentials positive to +30 mV it also induced a noisy outwardly rectifying current [I(BK(Ca))] that was abolished by iberiotoxin (0.1 microM). Inhibition of I(Ktotal) by propafenone was concentration-dependent (EC50 = 0.059 +/- 0.009 microM). Propafenone also inhibited the transient outward current [I(K(A))] and ATP-sensitive potassium current [I(K(ATP))] induced by levcromakalim (10 microM). Inhibition of I(K(V)), I(K(A)), and I(K(ATP)) by propafenone was voltage-independent. In Ca(2+)-containing conditions propafenone inhibited I(K(V)) and I(BK(Ca)) and immediately abolished spontaneous outward transient K+ currents. In whole veins, propafenone behaved as the K(V) inhibitor 4-aminopyridine, increasing the amplitude and duration of spontaneous contractions. Propafenone also inhibited the inhibitory effects of the K(ATP) channel opener levcromakalim on spontaneous contractions. These results indicate that in vascular smooth muscle cells, propafenone inhibits K(V), K(A), BK(Ca), and K(ATP) channels. These actions correlated with its effects on mechanical activity in whole portal veins.

Animals↗
PubMed2000

Accuracy of fine-needle aspiration biopsy of the thyroid combined with an evaluation of clinical and radiologic factors.

Fine-needle aspiration biopsy (FNAB) of thyroid nodules is an operator-interpreter-dependent procedure whose diagnostic accuracy has deficiencies, especially concerning indeterminate and negative results. There are reports in the literature of up to a 15% definitive diagnosis of carcinoma in the first category of cytology and an 11% false-negative rate in the second category. With these facts in mind, a prospective study was done at the Instituto Nacional de Cancerología, Mexico City, to determine whether one or several clinicoradiologic factors were associated with a final pathologic diagnosis of carcinoma, thereby increasing the diagnostic accuracy of thyroid FNAB. In total, 200 cases were reviewed, and 159 patients underwent surgery. Our study group comprises these 159 patients. The only clinical factor associated with false-negative results was size > or = 4 cm, with no statistical significance for the other factors analyzed. A comparison was done between clinical factors of patients who had indeterminate results in the aspirate and those of patients who had a definitive diagnosis by permanent section of the thyroid carcinoma, where an association was found between malignancy and tumor size > or = 4 cm, irregular borders, fixed lesions, and heterogeneity on ultrasound. We conclude that in the presence of a negative cytology result, with tumor size > or = 4 cm, close follow-up is indicated, and a new thyroid FNAB should be performed in 6 months. If the nodule persists or grows, a surgical procedure should be considered. In the case of an indeterminate cytology result and in the absence of those factors associated more frequently with a pathologic result of carcinoma, a conservative approach could be indicated with clinical follow-up and repeat thyroid FNAB in 6 months to 1 year.

Adult↗
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↗
PubMed2000

Prevalence of cutaneous manifestations in 200 patients with eating disorders.

BACKGROUND: Eating disorders are increasing and show a variety of symptoms. They mainly include anorexia nervosa (AN), bulimia nervosa (BN), and eating disorders not specified (EDNOS). They predominate in females and represent an important danger, especially in teenagers. In serious cases, they may be life-threatening. Objective To determine the prevalence of cutaneous findings in patients with eating disorders and to compare the results with those found in the literature. METHODS: An observational, transverse, and prospective study was performed. Two hundred patients of recent admission to ALUBA (association that fights against BN and AN), a psychiatric unit for eating disorders, were included: 122 BN; 62 AN; 16 EDNOS. RESULTS: Patients with eating disorders show dermatologic manifestations (alopecia, xerosis, hypertrichosis, caries, nail fragility) that are secondary to starvation. Russell's sign, seen as calluses on the dorsal aspect of the hands, is a consequence of self-induced vomiting and the local trauma of the superior incisors. This sign represents a compensatory behavior to overeating and predominates in the BN group. CONCLUSION: The recognition of dermatologic signs could be of immense value and could lead to the early diagnosis and treatment of these eating disorders.

Adolescent↗
PubMed1999

Effects of nicorandil as compared to mixtures of sodium nitroprusside and levcromakalim in isolated rat aorta.

1. The contribution of the relaxant mechanisms of nicorandil (NIC) were analysed by comparing its effects with those of sodium nitroprusside (SNP), levcromakalim (LEM) and mixtures (1:10, 1:30 and 1:100) of SNP:LEM in isolated endothelium-denuded rat aorta. 2. In rings precontracted with KCl (25 mM), the relative inhibitory potency of the soluble guanylate cyclase inhibitor ODQ and the K(ATP) channel inhibitor glibenclamide (GLI) on SNP:LEM mixtures showed a good correlation with the relative proportion of SNP and LEM in the mixtures. Furthermore, the degree of the inhibition by ODQ and GLI of the effects of the 1:30 SNP:LEM mixture varied as a function of the relative potency of SNP and LEM in KCl-, noradrenaline- (NA) or NA plus nifedipine-treated arteries. 3. The inhibitory effects of ODQ, GLI and ODQ plus GLI on NIC-induced relaxation was similar to that for the 1:30 SNP:LEM mixture in NA plus nifedipine-contracted arteries, but the inhibition of GLI or ODQ plus GLI was smaller in KCl-contracted arteries. 4. In conclusion, the relative importance of activation of the cyclic GMP pathway and K(ATP) channel opening in mixtures of SNP and LEM could be predicted by the proportion of the drugs in the mixtures and by the relative potency of SNP vs LEM in different experimental conditions. Furthermore, the present results suggest that besides these two mechanisms, a third ODQ- and GLI-insensitive mechanism, possibly involving Ca2+ channel blockade, also participates in the relaxant effects of NIC in KCl-induced contractions.

Animals↗
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↗
PubMed1999

Vasodilator effects of sodium nitroprusside, levcromakalim and their combination in isolated rat aorta.

1. The endothelial modulation of the relaxant responses to the nitric oxide (NO) donor sodium nitroprusside (SNP) and the KATP channel opener levcromakalim (LEM) and the interactions between these agents were analysed in isolated rat aorta. 2. LEM-induced relaxation was unchanged by endothelium removal or by the presence of L-NAME (10-4 M) or ODQ (10-6 M). In contrast, in KCl- (25 mM), but not in noradrenaline- (NA, 10-6 M) contracted arteries, SNP-induced relaxation was augmented by endothelium removal but not by L-NAME, indomethacin, glibenclamide nor charybdotoxin plus apamin. 3. The isobolographic analysis of the interactions between exogenously activated KATP channels and cyclic GMP using mixtures of SNP and LEM revealed that there were no interactions between both drugs at the proportions at which both drugs were active. However, the points for the SNP : LEM mixtures in proportions 10:1 and 1:10,000 (i.e. at concentrations at which LEM and SNP were inactive, respectively) fell significantly above the line of additivity indicating that there were negative interactions between both drugs at these selected proportions (about 5- and 2 fold inhibition, respectively). The former interaction was sensitive to glibenclamide, whereas the latter was insensitive ODQ. The magnitude of the 10:1 SNP:LEM interaction was smaller in endothelium-intact arteries and was absent in arteries stimulated by NA. 4. In conclusion, the relaxations induced by LEM and SNP were additive. However, the presence of endothelium and low concentrations of LEM inhibited SNP-induced relaxation. Both inhibitory effects were not additive and were only observed in KCl- and not in NA-contracted aortae.

Adenosine Triphosphate↗
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↗