Hyperglycemia increased the responsiveness of isolated rabbit's pulmonary arterial rings to serotonin.
The effect and mechanism of action of serotonin (5-HT) were studied in the pulmonary circulation of normal and diabetic rabbits. 5-HT (10, 50 and 100 nmol/l) produced a concentration-dependent increase in rabbit pulmonary arterial tension. Pulmonary arterial rings from diabetic rabbits were more responsive to 5-HT compared to those from normal rabbits. The pressor effects of 5-HT in normal and diabetic pulmonary arterial rings were totally abolished by either the 5-HT receptor antagonist, ketanserin (200 nmol/l) or the calcium channel blocker, verapamil (5.5 nmol/l). On the other hand, the cyclo-oxygenase inhibitor, indomethacin (0.4 nmol/l), significantly potentiated the pressor response of 5-HT in normal but not in diabetic pulmonary arterial rings. The lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 20 nmol/l), significantly enhanced the 5-HT-induced pressor response in normal rings while significantly attenuating those responses in diabetic rings. NG-nitro-L-arginine methyl ester (100 nmol/l), an inhibitor of nitric oxide synthase, significantly potentiated the contractile response of 5-HT in normal as well as diabetic pulmonary arterial rings. The results of this study indicate that 5-HT induces pulmonary hypertension in normal as well as in diabetic rabbits. In addition, experimentally induced diabetes exaggerates the pressor response of 5-HT and therefore may increase the risk of pulmonary hypertension. Furthermore, 5-HT alone or in combination with indomethacin, NDGA and a nitric oxide synthase inhibitor may be used to induce experimental pulmonary hypertension and possibly pulmonary edema.
el-Kashef
H
H
Department of Pharmacology, Faculty of Pharmacy, Mansoura University, Egypt.
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D012701:Serotonin; D009637:Masoprocol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin