Comparison of the Effects of Selective III, IV and Nonselective Phosphodiesterase Inhibitors on Isolated Tracheal Preparations in Streptozotocin-Diabetic Rats

Usta, Coşkun; Sadan, Gulay

doi:10.1159/000028340

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…Functional evidence suggests that both PDE III and PDE IV regulate cAMP, whereas PDE V regulates cGMP levels in guinea pig trachea [23,24]. PDE V is cGMP specific and has been shown to be expressed in skeletal, cardiac and smooth muscle preparations including vascular and tracheal smooth muscle.…”

Section: Discussionmentioning

confidence: 99%

Effects of Phosphodiesterase V Inhibition on Nitric Oxide-Mediated Relaxation Responses in Guinea Pig Trachea

Tuncel

Sadan²

2004

Pharmacology

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In the present study, we aimed to evaluate the effects of PDE V inhibition on NO-mediated relaxation responses in isolated guinea pig trachea. Under the NANC conditions, tracheal preparations were contracted with histamine (100 µm/l). When contraction had reached a plateau, relaxation responses to electrical field stimulation (EFS, 60 V, 0.5 ms, 5–10 Hz) were determined before and after incubation of the tracheal ring with L-NAME (1 mmol/l), a NO synthase inhibitor. L-NAME significantly inhibited the relaxation responses and this inhibitory effect was reversed by L-arginine (1 mmol/l), a precursor of NO, but was not affected by D-arginine. In addition, cumulative application of the NO donors, 3-morpholino-sydnonimine (SIN-1) and sodium nitroprusside (SNP), caused concentration-dependent relaxation of tissues precontracted with histamine. The selective PDE type V inhibitor zaprinast at EC₅₀ concentration (30 µmol/l) significantly potentiated EFS-induced NANC relaxations and relaxant responses to SIN-1 and SNP. In conclusion, these data support the hypothesis that NO is a mediator of NANC relaxations of guinea pig tracheal rings and PDE V inhibition potentiates NO-mediated relaxation.

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Section: Discussionmentioning

confidence: 99%

Effects of Phosphodiesterase V Inhibition on Nitric Oxide-Mediated Relaxation Responses in Guinea Pig Trachea

Tuncel

Sadan²

2004

Pharmacology

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“…Modifications in responses to several agents in various tissues from diabetic rats have been well‐documented (Morrison, Mackinnon, Bartrup, Skett & Stone, 1992; Kaputlu, Ozdem, Udan & Gökalp, 1999; Özdem, Adan, Usta & Tasatargil, 2000; Usta & Adan, 2000). Accordingly, changes in inotropic and chronotropic actions of adenosine in diabetic rat atria were also reported (Carrier, Edwards & Aronstram, 1984; Wichelhaus, Adan, Usta & Tasatargil, 1994).…”

Section: Introductionmentioning

confidence: 99%

The effects of adenosine on isolated right atrial preparations from streptozotocin‐diabetic rats

Usta

Adan

Özdem

2001

Journal of Autonomic Pharmacology

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1. The aim of the present study was to investigate the inhibitory effects of adenosine on the contractile force and chronotropic action of isolated right atrial preparations from streptozotocin (STZ)-diabetic rats. 2. The rats were anaesthetized with diethyl ether and STZ (65 mg kg(-1)) was injected intravenously via the tail vein. 3. Adenosine produced concentration-dependent decreases in the force of contraction and a negative chronotropic action of atria both in control and diabetic groups. The inhibition responses to adenosine were significantly higher in diabetic rat atria than control. 4. Dypiridamole incubation caused a significant potentiation of the inhibitory effect of adenosine on contractile force and chronotropic action of atria in the control group, but not in the diabetic group. In the presence of dipyridamole, the inhibitory effects of adenosine on measured parameters in diabetic rats were not significantly different from those in control rats. 5. These results suggested that atria from 6 weeks STZ-diabetic rats exhibited a supersensitivity to the negative inotropic and chronotropic effects of adenosine compared with atria from control rats because of an impairment in adenosine uptake mechanism. Altered sensitivity to effects of adenosine might reflect relatively early changes in the course of diabetes.

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Comparison of the Effects of Selective III, IV and Nonselective Phosphodiesterase Inhibitors on Isolated Tracheal Preparations in Streptozotocin-Diabetic Rats

Cited by 2 publications

References 16 publications

Effects of Phosphodiesterase V Inhibition on Nitric Oxide-Mediated Relaxation Responses in Guinea Pig Trachea

Effects of Phosphodiesterase V Inhibition on Nitric Oxide-Mediated Relaxation Responses in Guinea Pig Trachea

The effects of adenosine on isolated right atrial preparations from streptozotocin‐diabetic rats

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