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Research was conducted to determine whether the apparent upregulation of the angiotensinergic and vasopressinergic mechanisms in the renin TGR rats may also affect blood pressure regulation in the hypovolemic state. Under control conditions and during blockade of central AT1 and V1 receptors, blood pressure and heart rate responses to hemorrhage were determined in TGR(MrEN2)27 rats and in their parent normotensive Hannover Sprague-Dawley strain. Results demonstrate the enhanced involvement of central V1 and AT1 receptors in the regulation of blood pressure during hypovolemia in TGR.

A study was conducted to investigate the functional contribution of angiotensin converting enzyme (ACE)-independent angiotensin (ANG) II-forming pathways in the hamster cardiovascular system with ANG I and (Pro11, D-Ala12)ANG I as substrates. The presence of functional ACE-independent ANG II-forming pathways in the hamster cardiovascular system was confirmed although their contribution ratio is small. Chymase and aprotinin-sensitive serine proteases appear to be responsible for the alternative ANG II formation.

A study was conducted on male mRen-2 transgenic rats to investigate the impact of salt loading on acute and chronic cardiovascular parameters and endocrine and body fluid electrolyte responses using a chronic blood pressure monitoring system. The findings provide further proof that central angiotensin systems are critical in the regulation of osmotic responsiveness and that the renin gene may be a candidate marker for salt-sensitive hypertension.

Direct radioimmunoassay for mouse submaxillary renin together with indirect enzyme-kinetic assay based on the generation of angiotensin I with modification of the pH optimum, were used to measure rat and mouse plasma renin activity, plasma renin concentration and plasma prorenin in transgenic hypertensive rats (TGR) before and after lisinopril. Results showed that both rat and mouse renin gene expression in the kidney increased with lisinopril. Thus TGR have circulating active rat and mouse renin and prorenin.

Research suggests that hormone estrogen affects the vasoconstrictor-vasodilator balance of the renin angiotensin system of rats, thereby protecting transgenic hypertension. Experiments featuringoophorectomized female rats which under estrogen treatment are described. Evidence indicates that the vasoconstrictor properties of biochemical angiotensin II are affected.

The endothelium and vascular smooth muscle function of the mesenteric resistance arteries of Ren-2 transgenic and Sprague-Dawley rats were analyzed by myographs. Ren-2 transgenic and control rats exhibited similar response to the vasoconstrictive action of angiotensin I and II. However, the mesenteric arteries of Ren-2 transgenic rats exhibited higher sensitivity to thromboxane while administration of acetylcholine and angiotensin II

The transgenic study of TGR(m-REN2)27 rats is an effective animal model of hypertension with a precise definition of the genetic defect. The presence of an additional renin gene causes the development of severe hypertension in these rats. The renin gene with its catalyzing function in the formation of the effector peptide angiotensin II significantly influences the blood pressure. The model shows that alterations within the external renin-angiotensin system may cause a phenotype of hypertension.

Comparative studies of in control and transgenic hypertensive TGR (mREN-2)27 rats reveal that individual tissue and whole body insulin sensitivity do not vary due to single-gene hypertension. Fasting concentrations of insulin, plasma glucose, triglycerides and free fatty acids and fasting rates of glucose generation in the liver are normal in the transgenic rats. Both control and transgenic rats exhibit similar levels of activated whole body glucose utilization during euglycemic hyperinsulinemic clamp. Brown and white adipose tissues and various skeletal muscles of control and transgenic rats exhibit similar glucose utilization indices.

Analysis of the association of steroid production with tissue renin in the adrenal cortex in transgenic rats under dietary sodium restriction conditions reveals that sodium restriction induces an increase in adrenal renin levels and aldosterone biosynthesis in the adrenal cortex. Sodium restriction also enhances adrenal renin mRNA levels but not the renal renin and plasma renin functions. Sodium restriction causes an increase in circulating and renal renin levels in the Sprague-Dawley (SD) rats but does not enhance the mineralocorticoid generation in SD rats.

Brain microdialysis of transgenic (TG) rats with the mouse renin gene (mRen-2d) to examine the central interaction of vasopressin (AVP) system with the renin-angiotensin (RAS) system on the basis of the influence of angiotensin II (ANG II) on AVP secretion, heart rate and blood pressure shows that the mRen-2d gene induces modifications in the AVP axis, ANG-AVP central interactions and AVP levels in the brain and pituitary. The gene also weakens the central endocrine and cardiovascular responses to the central ANG (1-7) and ANG II levels due to the modification in the pituitary and brain AVP levels. ANG-II infusion elevates blood pressure, AVP secretion from supraoptic and paraventricular nuclei and causes a 22-fold increase in the AVP levels of dorsal lower brain stem.

The vascular renin-angiotensin (ANG) system does not couple with sympathetic nervous system locally, but high concentrations of ANG II, induced by circulation-derived renin, extend the period of sympathetic nerve-induced vasoconstriction. Exogenous renin increases vascular ANG release and prolongs pressor responses to nerve stimulation. Vascular renin regulates peripheral resistance.

A transgenic rat strain containing the mouse ren-2 renin gene (TGR(mRen2)27) facilitates the analysis of the influence of renin angiotensin system dysfunction in kidney and on modulation of blood pressure. It is indicated that mechanisms through which mouse renin transgene influences the kidney are not exclusively affected by hypertension. Transgenic rats exhibit transgene regulation which is influenced by age.

The monogenetic model transgenic (TG) rats carrying the mouse Ren-2 gene (ren-2d)27 were established by hypertension research. A 13-day therapy was performed to observe plasma levels of angiotensin (ANG) peptides in mature female TG-hypertensive and Sprague-Dawley rats. In this type of hypertension, the long term antihypertensive effects of the hindrance of angiotensin converting enzyme AT1 receptor blockade hypertension in female rats was mediated by the RAS.

A study of adult transgenic mRen-2 (TG) rats involved the determination of the hypertension by focusing on the renin-angiotensin system (RAS) activity, the sympathetic activity and the renal handling system. Age-matched Lyon genetically hypertensive rats (LH) were compared with TG rats. In conscious, freely-moving animals, the blood pressure (BP), the renal sympathetic nerve activity (RSNA) and the heart rate were measured. The RAS continues to be connected with the maintenance of high BP because the inclination for sodium and water retention is greater in adult TG rats than in LH rats.

A rat gene map was constructed using 174 distinct rat sequences derived from public data bases to generate sequence tagged microsatellite sites (STMSs) through polymerase chain reaction techniques. Since the 174 loci represented mostly protein coding regions, the resulting map is also a gene map. The analysis showed that STMSs with more than 10 repeats of each motif were more likely to be polymorphic. The microsatellite loci were also highly stable, making them amenable for linkage studies. The results showed that the use of STMSs is a powerful method for resolving the rat gene map.