Reduced activation and affinity of renin during pregnancy and oral contraception: determination of kinetic parameters by a fully autologous plasma renin assay.
In healthy normotensive pregnancy, a complex functional network develops between the cardiovascular system, the volume and composition of the extracellular fluid and the renin-angiotensin system (RAS). Cardiac output and heart rate increase, but blood pressure is reduced. The kidneys increase in size and both the glomerular filtration rate and renal blood flow increase early. Renal tubular water and sodium reabsorption is even more enhanced, so that the total body water of mother and foetus rises in the course of pregnancy by 6-8 litres. Plasma osmolality falls by about 10 mosm/kg. yet total body sodium increases by about 1 mol. Understandably, in the face of such complex fluid and pressure adjustments, data on the changes of the RAS in normal pregnancy are often contradictory. However, there is general agreement that the angiotensinogen and inactive renin in plasma are greatly raised. Most groups have also found a considerable increase in active renin. These changes could lead to higher rates of angiotensin I (AI) formation (and hence high circulating angiotensin II levels), with adverse consequences for mother and foetus. The high proportion of inactive renin may reflect a reduction in the rate of activation of prorenin in order to avoid these consequences. This reduction may involve kallikreins which have been listed amongst the putative in vivo activators of prorenin. Excessive AI formation in pregnancy could also be avoided by the production of functionally different renins or angiotensinogens. Such changes will be difficult to detect with assays which require addition of extraneous renin or angiotensinogen.(ABSTRACT TRUNCATED AT 250 WORDS)