Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene

Article Abstract:

Essential hypertension, which is elevated blood pressure with no obvious cause, is a leading cause of death due to cerebral hemorrhage, heart disease and kidney failure. Essential hypertension is thought by many to be a complex condition involving the interaction of several genes with environmental factors. Although the renin-angiotensin system is thought to be important in the regulation of blood pressure, it is not clear if or how this regulatory system might be disturbed in patients with essential hypertension. Ren-2 is a special renin gene obtained from mice that causes the secretion of renin in mouse salivary glands. It had already been determined that injections of mouse Ren-2 protein could cause hypertension in rats. The mouse Ren-2 gene was injected into fertilized rat eggs, which were implanted in the uterus of female rats and carried to term. (Animals that contain genes taken from other animals are called transgenic.) Five rats were born carrying the Ren-2 gene; at maturity, four of these bred successfully. Rats carrying the gene developed hypertension rapidly, beginning at about four weeks of age. Although the rats carried the extra renin gene, they did not have elevated levels of plasma renin; in fact, renin and angiotensin I were significantly lower in the transgenic rats. In this way the rats resemble human patients with essential hypertension, who usually have normal or reduced levels of renin. On possible explanation for the hypertension is that the extra renin gene results in the overproduction of steroid hormones in the adrenal cortex. Although preliminary evidence has found elevated aldosterone in the urine of male transgenic rats, this possibility needs to be fully evaluated. The Ren-2 transgenic rats clearly provide an opportunity to study the role of renin in the regulation of blood pressure, which is apparently a more subtle process than had been previously supposed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Renin

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Hypertension: stress on the renin gene

Article Abstract:

The renin-angiotensin system is believed to play a role in the regulation of normal blood pressure. The common understanding of this system is that renin is released by the kidney, which acts upon angiotensinogen produced by the liver. The resulting angiotensin I may be converted by angiotensin converting enzyme to angiotensin II, which stimulates the smooth muscle of arteries to contract. However, this conventional model shows its weakness when attempts are made to understand the physiological mechanisms of essential hypertension, or high blood pressure with no obvious cause. Researchers have now shown that providing laboratory rats with a second renin gene, in this case a slightly different version obtained from mice, results in the rats developing hypertension. Since the injection of renin is known to cause hypertension, this result is not surprising on its surface. What is interesting is that, although the rats develop hypertension, their blood levels of renin and angiotensin are normal. This is also the case with human essential hypertension. These hypertensive rats also resemble human patients in that their hypertension develops slowly as they mature. However, it is not yet clear that this new model of hypertension is not more closely related to other, more rare, forms of hypertension such as that resulting from adrenal hyperplasia. It is certain that the feedback mechanisms controlling the renin-angiotensin system are as complex as they are important; the novel rat model may help unravel the complicated picture of how a multitude of genes interact with the environment in the pathogenesis of hypertension. (Consumer Summary produced by Reliance Medical Information, Inc.)

editorial

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Dominant negative mutations in human PPAR-gamma associated with severe insulin resistance, diabetes mellitus and hypertension

Article Abstract:

It has been possible to identify the first examples of naturally occurring loss-of-function germline mutations in human PPAR-gamma. There is a strong association between these mutations and an unusual syndrome of strong insulin resistance, early onset diabetes and hypertension. It is possible that residual PPAR-gamma activity, possibly controlled by high endogenous ligand concentrations in adipocytes, is sufficient to maintain adipogenesis. There is a possible causal connection between the PPAR-gamma mutation and early onset hypertension through effects on vascular tone.

Diabetes, Diabetes mellitus, Insulin resistance

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