Chemical sympathectomy and serotonin inhibition reduce monocrotaline-induced right ventricular hypertrophy in rats.
Young male rats were administered monocrotaline (40 mg/kg, s.c.) either after chemical sympathectomy with 6-hydroxydopamine (6-OHDA, 100 mg/kg), after serotonin synthesis inhibition with p-chlorophenylalanine (PCPA, 500 mg/kg), or after saline injection. Monocrotaline rats exhibited a loss of body weight, marked right ventricular hypertrophy (RVH), increased pulmonary vascular muscularization, but no change in left ventricular weight or hematocrit at 20 days post-monocrotaline. Pretreatment with 6-OHDA or PCPA reduced the degree of RVH; however, neither 6-OHDA nor PCPA pretreatment prevented or reduced the pulmonary vascular muscularization associated with monocrotaline. Control, 6-OHDA-, and PCPA-treated rats exhibited only changes in ventricular weights associated with changes in their body growth. Thus, the sympathetic nervous system and serotonergic mechanisms seem to be involved in the development of monocrotaline-induced right ventricular hypertrophy, but are not responsible for the pulmonary vascular lesion.
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced*; D010134:Fenclonine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D008168:Lung / Q000098:blood supply; D008297:Male; D016686:Monocrotaline; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D016627:Oxidopamine; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013563:Sympathectomy, Chemical
D006892:Hydroxydopamines; D011763:Pyrrolizidine Alkaloids; D012702:Serotonin Antagonists; D016686:Monocrotaline; D016627:Oxidopamine; D010134:Fenclonine