In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18alpha-gl...

The current study addressed two important concerns, one pertinent to the impact of PDE-5 inhibitor (tadalafil) on morphine-induced analgesia and the second relevant to its influence on morphine-induced oxidative stress in two different pain models, the the tail-flick test (representing an acute thermal phasic pain model ) and the formalin test (representing an inflammatory tonic pain model ). T...

Gustafsson, Åsa B., and Laurence L. Brunton. Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1 and NO: role of cGMP-stimulated PDE2. Am J Physiol Cell Physiol 283: C463–C471, 2002; 10.1152/ajpcell. 00299.2001.—Treatment of cultured adult rat cardiac fibroblasts with interleukin-1 (IL-1 ) induces the inducible nitric oxide synthase (iNOS) expression, increases nitric oxid...

Previous studies have shown reduced effects of cAMP-dependent positive inotropic agents in the failing human myocardium; thus other cAMP-independent mechanisms of action may be useful to increase force of contraction in this condition. The purpose of this investigation was to determine whether a positive inotropic effect of the cAMP-phosphodiesterase (PDE) inhibitor pimobendan is observed in th...

Treatment of cultured adult rat cardiac fibroblasts with interleukin-1beta (IL-1beta) induces the inducible nitric oxide synthase (iNOS) expression, increases nitric oxide (NO) and cGMP production, and attenuates cAMP accumulation in response to isoproterenol by ~50%. Reduced cAMP accumulation is due to NO production: the effect is mimicked by NO donors and prevented by N(G)-monomethyl-L-argini...

Various anti-inflammatory drugs have been used for treatment of neonatal meconium aspiration syndrome (MAS). As their adverse effects are poorly described, this study compared effects of selective phosphodiesterase (PDE) 3 inhibitor olprinone and non-selective PDE inhibitor aminophylline on cardiovascular parameters in animal model of MAS. Oxygen-ventilated rabbits were intratracheally instille...

Phosphodiesterase (PDE) is a critical regulator of cAMP/protein kinase A (PKA) signaling in cells. Multiple PDEs with different substrate specificities and subcellular localization are expressed in neurons. Dopamine plays a central role in the regulation of motor and cognitive functions. The effect of dopamine is largely mediated through the cAMP/PKA signaling cascade, and therefore controlled ...