Bulent Sarac

Vasorelaxing properties of some phenylacridine type potassium channel openers in isolated rabbit thoracic arteries.

In this study, 12 new 2,2,7,7-tetramethyl-9-aryl-2,3,4,5,6,7,9,10-octahydro-1,8-acridindione derivatives were synthesised and their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rabbit thoracic arteries was investigated. Pinacidil was used as standard potassium channel openers in this study. Compounds 1-12 and pinacidil exerted concentration-dependent relaxation responses precontracted phenylephrine in the aortic rings with the efficacy order: 11>pinacidil>7>2>8>3>1>4>10>6>9>5>12.

Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro

Background. The aim of this study was to investigate the role of omeprazole and lansoprazole, H+-K+ ATPase inhibitors, in gallbladder smooth muscle contractility in vitro. Methods. Gallbladder muscle strips obtained from guinea pigs were mounted in an organ bath. The responses of both precontracted strips and strips under basal tension to omeprazole and lansoprazole were determined. Results. Spontaneous contractile activity was blocked following omeprazole and lansoprazole administration. The agents also caused concentration-dependent relaxation in carbachol- and KCl-precontracted gallbladder muscle strips. Pretreatment with atropine (1 µM), NW-nitro l-arginine methyl ester (l-NAME; 30 µM), indomethacin (10 µM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethylammonium chloride (0.5 mM), glibenclamide (1 µM), 4-aminopyridine (0.1 mM), or clotrimazole did not inhibit this relaxation. Gallbladder strips were placed in high-concentrtion potassium (80 mM), calcium-free solution. The contraction produced with the addition of Ca2+ (2.5 mM) was completely relaxed by omeprazole, lansoprazole, and nifedipine separately. Conclusions. These results demonstrate that omeprazole and lansoprazole have potent inhibitory effects on spontaneous contractions and cause dose-dependent relaxation in precontracted gallbladder smooth muscle strips of guinea pig in vitro. This effect could be due to blockade of the calcium channels.

The evaluation of the effects of renal failure on erectile dysfunction in a rabbit model of chronic renal failure.

To determine whether chronic renal failure (CRF) reduces nitrergic relaxant responses in a rabbit model.

Effect of chronic renal failure on the purinergic responses of corpus cavernosal smooth muscle in rabbits

Objective  To examine purinergic relaxation responses in chronic renal failure (CRF) in an experimental rabbit model, and thus evaluate the possible involvement of the purinergic system in erectile dysfunction with CRF.

Effect of hypothyroidism on the NO/cGMP pathway of corpus cavernosum in rabbits.

INTRODUCTION The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. There is some evidence suggesting that hypothyroidism may be a cause of impotence. AIM We aimed to investigate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in hypothyroidism in an experimental rabbit model and compared hypothyroid rabbits with controls to evaluate the possible involvement of the NO/cGMP pathway. METHODS The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. The first group had hypothyroidism induced surgically by thyroidectomy for 6 weeks. The second group underwent a sham operation. RESULTS There was no significant change in the mean body weight of hypothyroid rabbits and controls. Triiodothyronine and thyroxine levels were significantly lower in hypothyroid rabbits. Plasma thyroid-stimulating hormone and prolactin levels were significantly higher in hypothyroid rabbits. Plasma total calcium and parathormone levels remained in the normal range in both groups. MAIN OUTCOME MEASURES Papaverine-induced concentration-dependent relaxations were similar in both groups. Carbachol-induced relaxation responses decreased in hypothyroid rabbits. There were significant differences between control and hypothyroid rabbits in frequency-dependent relaxations induced by electrical-field stimulation (EFS). YC-1-induced relaxation responses did not change significantly in hypothyroid rabbits. Concentration-dependent relaxations induced by diethylamine (DEA)/NO were similar in both groups. Amrinone-induced relaxation responses did not change significantly in hypothyroid rabbits. CONCLUSION Reductions of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on the decrease of released or synthesized NO from nitrergic nerves and endothelium.

The effect of chronic renal failure on phosphodiesterase inhibitor-induced relaxation responses in rabbit cavernosal strips.

Erectile dysfunction is common in men with chronic renal failure. Previously nitrergic and endothelium-dependent relaxation responses have been shown to be reduced in chronic renal failure rabbits. We have therefore investigated the efficacy of phosphodiesterase inhibitors on the corpora cavernosa obtained from uremic rabbits. Uremia was induced with 5/6 nephrectomy and 4 weeks later cavernosal tissue strips were isolated. The relaxant effect of phosphodiesterase 5 inhibitors, zaprinast (1-300 microM) and sildenafil (0.01-300 microM), phosphodiesterase 3 inhibitor amrinone (1-100 microM) and non-specific phosphodiesterase inhibitor papaverine (1-300 microM) were investigated on phenylephrine (10 microM)-induced tone. We found a shift in the dose-response curve of only phosphodiesterase 5 inhibitors. These results suggest that the decreased production or availability of endogenous nitric oxide in chronic renal failure animals leads to decreased efficacy of phosphodiesterase 5 inhibitors to induce relaxation.

In vitro effects of intravenous anesthetics on the sphincter of oddi strips of sheep

Background: Intravenous anesthetics are often used for conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi (SO) manometry. This study was designed to investigate the direct effects of some intravenous anesthetics on SO in sheep. Methods: In sheep SO rings, changes in isometric tension in response to cumulative concentrations of intravenous anesthetics were determined, and values for E_max (mean maximal inhibition) and pD₂ (i.e. the negative logarithm of the concentration for the half-maximal response, EC₅₀) were compared. Results: Meperidine (10^–7 to 3 × 10^–5M), fentanyl (10^–7 to 3 × 10^–5M), midazolam (10^–7 to 3 × 10^–5M) and propofol (10^–7 to 3 × 10^–4M) induced concentration-dependent relaxations on SO precontracted with carbachol (10^–6M). E_max and pD₂values following meperidine, fentanyl and midazolam administration were significantly greater than after propofol (p < 0.05). There were no significant differences in E_max and pD₂values for meperidine, fentanyl and midazolam. Conclusion: These results suggest that meperidine, fentanyl and midazolam are equipotent relaxants in the sheep SO in vitro. The relaxatory effect of propofol was 10 times less potent compared to the above agents, and it can be beneficial during SO manometry in controlled clinical human studies.

Comparative relaxant effects of YC-1 and DEA/NO on the sheep sphincter of Oddi

Background/Aims: Nitric oxide (NO) is a major inhibitor in various parts of the gastrointestinal tract. This study was designed to compare the effects of YC-1, NO-independent soluble guanylate cyclase (sGC) activator, and DEA/NO, NO-nucleophile adduct, on sheep sphincters of Oddi (SO). Methods: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1, 10^–10–10^–5M), diethylamine/NO complex (DEA/NO, 10^–8–10^–4M). We also evaluated the effect of YC-1 (10^–6 and 10^–5M) and DEA/NO (10^–5 and 10^–4M) on the levels cyclic GMP (cGMP) in isolated SO. Results: YC-1 (10^–10–10^–5 M) and DEA/NO (10^–8–10^–4M) induced concentration-dependent relaxation of isolated SO rings precontracted with carbachol (10^–6M). The pEC₅₀ value of DEA/NO was significantly lower than those for YC-1 (p < 0.05), with no change of E_max values. YC-1 increased cGMP levels more than control, carbachol and DEA/NO groups (p < 0.05). Conclusion: These results show that YC-1 is a more potent relaxant than DEA/NO and causes more elevation of cGMP levels in isolated SO rings.

Hydrogen-potassium ATPase inhibitors induce relaxation on rabbit prostatic strips in vitro

Background : To determine the relaxant effect of omeprazole and lansaprazole, hydrogen–potassium (H+–K+) ATPase inhibitors, on rabbit prostatic tissue in vitro.

DO ANTIBIOTICS CONTRIBUTE TO POSTOPERATIVE ILEUS? CONTRACTILE RESPONSES OF ILEUM SMOOTH MUSCLE IN GUINEA PIGS TO LONG-TERM PARENTERAL CEFTRIAXONE AND AMPICILLIN

Background:  Antibiotics may impair small bowel smooth muscle contractility and contribute to postoperative ileus. The aim of this study was to compare the contractile responses of ileum smooth muscle to different agonists in guinea pigs treated with ceftriaxone (Rocephin; F. Hoffman–La Roche, Kaiseraugst, Switzerland) or ampicillin (Ampisina; Mustafa Nevzat İlaç Sanayii AŞ, Istanbul, Turkey).