Angiotensin system, for hypertension

FIGURE 27.7 DMLs targeting the Angiotensin system for hypertension. 

The interest in these peptides and others whose mechanisms of action are not yet so clearly defined is evident from the many recent publications. Since the peptides are not orally active, their role in the treatment of hypertension is uncertain at this point. Their value as diagnostic tools has been established. For example, the use of saralasin in the recognition of angiotensinogenic hypertension in man has been demonstrated (103). Perhaps of greater value will be the role of these compounds and peptides still to come in defining the importance of the renin-angiotensin system in the etiology of hypertension and the control of blood pressure. 

There is a hypothesis that irregularity of the rennin-angiotensin system lies at the base of etiology of all cases of essential hypertension. However, despite all of the apparent attractiveness of this theory, there is still not enough proof for it to be accepted as the single reason of elevated arterial blood pressure. 

Particularly when androgens/anabolics are misused to promote extreme muscular development, there is a risk of cardiomegaly and ultimate cardiac failure. Androgen-induced hypertension may be due to a hypertensive shift in the pressure-natriuresis relation, either by an increase in proximal tubular reabsorption or by activation of the renin-angiotensin system (27). This effect is not related to higher doses or longer treatment and can develop after a few months but can also be delayed for many years. 

The renin-angiotensin system (RAS) controls both vasoconstriction and fluid retention (Scheme A.2). Increasing either vasoconstriction or fluid retention increases blood pressure. Although complex, the RAS has been thoroughly studied, is well understood, and provides a number of pharmaceutical targets for managing hypertension. 

---