Angiotensinogen is the only known precursor to the angiotensin peptides, which are important regulators in the control of blood pressure. Although the major source of circulating angiotensinogen is the liver, preliminary studies have demonstrated that adipose tissue of the rat is the largest extra- hepatic source of angiotensinogen messenger RNA (mRNA). Angiotensinogen mRNA is present in both brown and white adipose tissue; this represents the first demonstration of any interaction between the renin-angiotensin system and adipose tissue. The general hypothesis of this proposal is to investigate interactions between the angiotensinogen-angiotensin system and adipose tissue, with emphasis on the possible implications of these interactions to cardiovascular control. The proposed research plan will investigate four specific hypotheses based on the presence of angiotensinogen mRNA in adipose tissue. Hormones which have previously been shown to regulate levels of angiotensinogen mRNA in rat liver preparations will be evaluated for their effects on adipose angiotensinogen mRNA levels. The hormones chosen for these experiments all have effects on fat metabolic and storage. To examine post- translational processing and secretion mechanisms of angiotensinogen in adipocytes, pulse-chase experiments will utilize incorporation of a labeled amino acid into angiotensinogen. The appearance of labeled angiotensinoge in the cells versus media of incubated adipocytes will be examined using SDS-polyacrylamide gel electrophoresis followed by a Western blot protocol. Characterization, of angiotensin II receptors on adipocyte membrane preparations ar effects of guanine nucleotide proteins on binding of angiotensin II to its receptor will be examined by using a saturation ligand binding assay. The contribution of angiotensin, released from adipose tissue, on facilitation of labeled neurotransmitter release will be evaluated in the perfused mesenteric artery. These studies will further our understanding of the possible role of angiotensinogen in adipose functions. Obesity is commonly associated with hypertension. In addition, the renin-angiotensin system has been implicated in the etiology of hypertension. The findings of the proposed study will help to elucidate the association between the presence of angiotensinogen mRNA in adipose tissue and obesity related hypertension.
| Cassis, L A (1993) Role of angiotensin II in brown adipose thermogenesis during cold acclimation. Am J Physiol 265:E860-5 |
| Soltis, E E; Jewell, A L; Dwoskin, L P et al. (1993) Acute and chronic effects of losartan (DuP 753) on blood pressure and vascular reactivity in normotensive rats. Clin Exp Hypertens 15:171-84 |
| Soltis, E E; Cassis, L A (1991) Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A 13:277-96 |
| Cassis, L A; Dwoskin, L P (1991) Presynaptic modulation of neurotransmitter release by endogenous angiotensin II in brown adipose tissue. J Neural Transm Suppl 34:129-37 |
