Monocrotaline-induced

Liu L, Liu H, Visner G, Fletcher BS. 2006. Sleeping beauty-mediated eNOS gene therapy attenuates monocrotaline-induced pulmonary hypertension in rats. FASEB J. 20 2594-2596. 

The AC activities due to the stimulation of p-receptors and Gs-proteins were increased in adriamycin-induced cardiomyopathy in rabbits (Calderone et al. 1991). On the other hand, no alterations in p-AR density, G-proteins, or AC activities were seen in adriamycin-induced cardiomyopathy in rats (Fu et al. 1991). Depressions in p-ARs and AC activities in the absence or presence of various stimulants were noted in catecholamine-induced cardiomyopathy in rats in addition to an increase and loss of Gi- and Gs-proteins, respectively (Meszaros and Levai 1992 Muller et al. 1993 Zhou et al. 1995). Rats with monocrotaline-induced right heart cardiomyopathy showed depressions in prAR density and AC activities in the presence... 

Yoshie, H., Tobise, K., and Onodera, S. 1994. Intraventricular changes in the P-adrenoceptor-adenylate cyclase system of the rat heart with the progress of monocrotaline-induced right ventricular hypertrophy. Jpn. Circ. J. 58 855-865. 

FIGURE 8.5 Proapoprotic experimental therapies in pulmonary arterial hypertension (PAH). A common denominator of these therapies is the induction of apoptosis as well as suppression of proliferation in the pulmonary artery wall. On the left are untreated rats with monocrotaline-induced PAH and on the right are rats treated with elastase inhibitors. Increased apoptosis of the intima-media is showed by TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling), and decreased proliferation is imaged by staining for proliferation cell nuclear antigen (PCNA). The same pattern has been shown in the media of treated rats by all the therapies shown in the box. (From Ref. 116, with permission.)... 

Caveolin (Cav), structural protein necessary and sufficient for the formation of caveolae. Cav-1 and Cav-3 are co-expressed in most cell types, including endothelial cells, epithelial cells, and fibroblasts, whereas Cav-3 are expressed by cardiomyocytes. However, smooth muscle cells express all three caveolins. It has been reported that administration of a cell-permeable Cav-1 prevents the development of monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy [T. Okamoto et al., J. Biol. Chem. 1998, 273, 5419 J.-F. Jasmin et al.. Circulation 2006, 224, 912]. 

Langleben, D., Carvalho, A.C.A. and Reid, L.M. (1986). The platelet thromboxane inhibitor, dazmegrel, does not reduce monocrotaline-induced pulmonary hypertension. Am. Rev. Respir. Dis., 133, 789-791... 

Campbell AIM, Kuliszewski MA, Stewart DJ. Cell-based transfer to the pulmonary vasculature endothelial nitric oxide synthase overexpression inhibits monocrotaline-induced pulmonary hypertension. Am J Respir Cell Mol Biol 1999 21 567-575. 

NagayaN, Yokoyama C, Kyotani S, Shimonishi M, et al. Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonaiy hypertension in rats. Circulation 2000 102 2005-2010. 

In our laboratory, dogs, rats, mice, and hamsters have been exposed to CAPs. We also have the capability to study various animal models of disease, including rats with monocrotaline-induced inflammation and chronic bronchitis, mice with asthma, and dogs with acute coronary occlusion to model an angina attack. These studies have provided the preliminary basis for investigations of the mechanisms of response described in the foregoing. 

Rat models of monocrotaline-induced pulmonary vascular injury-inflammation (120,121) and chronic bronchitis, with their appropriate controls have been used in exposures of groups of 16 animals to CAPs and groups of 16 normal or diseased animals exposed to filtered air at the same temperature, pressure, and flow, as a control. The concentration factor of outdoor air particles was approximately 30-fold. Exposures to CAPs resulted in significant mortality with monocrotaline-induced inflammation and significant mortality in animals with chronic bronchitis. Table 2 lists concentration, mortality, and pathological findings in these studies (21). 

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