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Introduction To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes. Methods The experiments were performed in Sprague Dawley rats using a hot-plate device. Streptozotocin (STZ) was administered to the rats after taking control measurements. Rats with a blood glucose level of 240 mg/dL or above in the blood specimen obtained from the tail vein 3 days after STZ administration were considered as being diabetic. Three weeks after STZ administration, the hot-plate test was performed. Compared with the control measurements, rats that exhibited >20% decrease in the second hot-plate test measurements were considered to have developed neuropathy. Drugs [mirtazapine, naloxone (opioidergic antagonist), metergoline (serotonergic antagonist), and BRL44408 (adrenergic antagonist)] and drug combinations were administered to those rats that developed neuropathy. After administrating the drugs or drug combinations, the third hot-plate test was performed. Results Mirtazapine at doses of 10 and 15 mg/kg exhibited a significant antinociceptive effect. Naloxone, metergoline, or BRL44408 alone did not cause an antinociceptive effect. However, combinations of these drugs with mirtazapine (15 mg/kg) significantly decreased the antinociceptive effect of mirtazapine. Conclusion It is suggested that mirtazapine has a significant antinociceptive effect in diabetic neuropathy and that opioidergic, serotonergic, and adrenergic systems have roles to play in this effect.

Preliminary clinical studies of testosterone therapy in male patients with coronary artery disease obtained promising results. However, little is known about the in vitro effects of testosterone in human isolated arteries. We investigated the effect of testosterone on contractile tone of human isolated radial artery (RA). Testosterone was added (0.1 – 300 µM ) cumulatively to organ baths after precontraction with KCl (45 mM) and phenylephrine (PE, 10 µM). Testosterone-induced relaxations were tested in the presence of the cyclooxygenase inhibitor indomethacin (10 µM), nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM), non-selective large conductance Ca2+-activated and voltage-sensitive K+ channel inhibitor tetraethylammonium (TEA, 1 mM), ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 10 µM), and voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM). Testosterone produced relaxation in human RA (Emax: 53.03 ± 2.76% and 66.83 ± 1.97% of KCl and PE-induced contraction, respectively). Except for GLI, the relaxation to testosterone is affected by neither K+ channel inhibitors (TEA, BaCl2, and 4-AP), L-NAME, nor indomethacin. We report for the first time that supraphysiological concentrations of testosterone induces relaxation in RA. This response may occur in part via ATP-sensitive K+ channel opening action. Keywords:: human radial artery, testosterone, vasodilation, potassium channel

Objective: Diabetes mellitus causes a decrease in cardiac output, arterial blood pressure, and heart rate. In this study, we aimed to investigate, at the molecular level, the effect of nitric oxide synthase (NOS) on heart pathology in type 1 diabetes and look at the therapeutic effect of pentoxifylline on this pathology., Objective: Diabetes mellitus causes a decrease in cardiac output, arterial blood pressure, and heart rate. In this study, we aimed to investigate, at the molecular level, the effect of nitric oxide synthase (NOS) on heart pathology in type 1 diabetes and look at the therapeutic effect of pentoxifylline on this pathology. Methods: In this experimental study, 50 Wistar albino male rats were used. The rats were divided into 5 groups: group C, control; group D, only diabetes; group D+PI and D+PII, diabetes + pentoxifylline; group P, only pentoxifylline. Group D+PI rats received 50 mg/kg/day pentoxifylline over two months. However, group D+PII rats received saline in the first month and 50 mg/kg/day of pentoxifylline over the following month. At the end of two months, NOS expressions in heart tissue were assessed through immunohistochemistry analysis. The data were compared by one-way ANOVA. Results: At the end of the experiments, there was increased cytoplasmic vacuolization, myofibrillar loss, cytoplasmic eosinophilia, and degeneration of cardiomyocytes; nNOS and iNOS expressions in group D decreased compared with that in group C. In group D+PI and group D+PII, nNOS and iNOS expressions improved compared with group D. Conclusion: As a result, we found that diabetes, a known chronic disease, causes serious damage in heart tissue. NOS plays a role in this damage, and pentoxifylline aided in improving nNOS and iNOS expression in this damage

Objective: To investigate the direct effects of dexmedetomidine (DEX) on isolated human internal mammary artery (IMA). Design: In vitro experimental study. Setting: Cardiovascular Pharmacology Laboratory, Department of Pharmacology, Gulhane School of Medicine, Ankara, Turkey. Participants: IMA segments were obtained from 18 patients undergoing coronary artery bypass surgery. Interventions: The response in IMA was recorded isometrically by a force displacement transducer in isolated organ baths. DEX-induced contractions were tested in the presence of the α2-adrenoceptor antagonist yohimbine (10−7 mol/L) and the α1-adrenoceptor antagonist prazosin (10−8 M). The effect of DEX (10−7, 10−6, and 10−5 mol/L) on phenylephrine (10−9-3 × 10−4 mol/L)-induced contactions was also tested. Measurement and Main Results: DEX (10−9 mol/L-3 × 10−5 mol/L) caused contraction in IMA segments. The contraction at lower concentrations of DEX (10−9 mol/L-3 × 10−7 mol/L) was attenuated by yohimbine (10−7 mol/L), whereas prazosin (10−8 mol/L) attenuated the contractions at higher concentrations of DEX (10−6 mol/L-3 × 10−5 mol/L). Incubation of IMA segments with high concentrations of DEX (10−6 mol/L and 10−5 mol/L) caused an inhibition of phenylephrine (10−9 mol/L-3 × 10−4 mol/L)-induced contraction. Conclusion: These data suggest that DEX causes contraction by activating α2-adrenoceptors at lower concentrations, but it may also activate α1-adrenoceptors at higher concentrations in IMA. The action of DEX on phenylephrine-induced contraction may be related to an α1-adrenoceptor antagonistic effect produced via partial α1-adrenoceptor agonistic action.