Primary Study Of Regulation Effects Of Agmatine On Pulmonary Artery Tension And Its Receptor Mechanisms In Rats

Li, et al separated a molecule from bovine brain cortex that could substitute clonidine and was approved as agmatine (AGM) in 1994. Agmatine is transformed by L-arginine in function of arginine decarboxylase. In recent years, researchers discovered that agmatine was extensively distributed in tissues of mammal. It major works on imidazoline receptors (IR), along with α2-adrenoceptor and can regulate certain neurotransmitter release. It has various biological activity such as decrease the blood pressure, reduce serum glucose,excrete the urine,antagonize the tolerance and the dependence of opioid agonists, all of these suggested that agmatine was a novel neurotransmitter or neuromodulator. However, the biological function, pathophysiological significance and mechanisms of agmatine still remain vague.Gao, et al( Life Science,1995) reported that agmatine is a novel endogenous vasoactive substances, which can cause arterial blood pressure in systemic hemodynamics and peripheral vascular resistance descent .The agmatine works in a way differ from bradykinin, isoprotcrcnoland, nitroglycerin. Further study showed that imidazoline receptors, especially I2R, distribute widely in human and animal body, contribute to the vsoactive effects of agmatine in systemic circulation. Agmatine can inhibit serum stimulated coronary arterial smooth muscle cell proliferation via imidazoline receptors. The previous studies have suggested that agmatine was an important endogenous modulator of vascular tone and vascular smooth cell proliferation.Hypoxic pulmonary hypertension is center link of high altitude pulmonary edema, high altitude heart disease and chronic pulmonary heart disease. The hypoxa induced pulmonary vasoconstriction and vascular remodeling are two ajor processes for the development of hypoxic pulmonary hypertension so, to illuminate the mechanisms of hypoxic pulmonary vascular constriction and vascular remodeling and looking for the prevention and cure measures are the important project in current research l field.It has been reported that pulmonary vascular tone and vascular smooth cell proliferation were mediated by circulating and local vasoactive factors such as nitric oxide, prostcycling, endothelin, angiotensin and etc. Study on the action and mechanisms of local vasoactive factors will greatly help us to better understand the development mechanism of hypoxic pulmonary hypertension.In recent years, the research shows that the abnormal metabolism of arginine and nitric oxide (NO) in pulmonary vascular endothelial cells and pulmonary vascular smooth muscle cells have the important function on the development of hypoxic pulmonary hypertension. NO, as a metabolized production from L-arginine via nitric oxide synthase (NOS), distributed widely and has various biological function in mediating vascular tone and vascular smooth cell proliferation. In vivo, L-arginine does not only transform into NO via nitric oxide synthase, but also transform to agmatine via arginine decarboxylase, and the latter is also an important metabolic pathway. The primary studies in the recent years show arginine decarboxylase and related receptor distributed in the pulmonary vascular endothelial cells?and pulmonary vascular smooth muscle cells. In the bovine cultured pulmonary artery endothelial cells, agmatine act on imidazoline I2R, induce Ca2+ transient response, make the production of NO increase by three tmes. This appears that agmatine play an important role in the regulation of pulmonary blood vessel functions. But many basic questions such as the regulation effects of agmatine on the pulmonary blood vessel, its mechanisms and the pathophysiological meanings?on pulmonary hypertension still lack of study.For future qualitative and semiquantitative research of agmatine by immunohistochemical method, we first produced rabbit polyclonal antibody of agmatine in the experiment, since no commercial antibody of agmatine can be purchased. Furthermore, we observed primarily the distribution of agmatine in pulmonary tissue by using immun...