Consequenlty, by many indirect measure, pregnancy is a normal -fill conditio.

For example, gravidae can excrete a water load and dilute their urine as well as nongravidae, and their circulatinf levels of AVP are comparable to nonpregnaant subjects (see Osmoregulation and renal Handling of Water section). In response to saline infusions, increase in urinary sodium excretion is comparable between pregnant and nonpregnant women. These observations contrast markedly with pathophysiological states of cirrhosis and congestive heart failure, in which despite the massive increases in extracelullar volume, there is decreased effective circulatory volume. These patients fail to excrete a water load or dilute th eir adequately. Basal levels of AVP are elevated, and sodium excretion in decreased. Finally in gravid rats, tubuloglomerular feedback sensitivity is not suppressed as would be expected in the face of the absolute increase in plasma volume, but is reset around the higher level of single nephron GFR during pregnancy. This observation suggest that the volume status of pregnancy is indeed perceived as normal-fill by the kidney. Interestingly, another mechanism for sodium retention in rat pregnancy is increased renal phosphodiesterase-5 activity that, in turn, decreases atrial natriuretic pepptide (ANP)-dependent cGMP accumulation, thereby impairing sodium excretion. However, wheter this mechanism partains to human pregnancy needs to be investigated because there does not appear to be an attenuation of the nitrauretic response to ANP. Moreover, the fractional excretion of cGMP increases from ~1.0 in the prepregnant (or post partum) state to ~2.0 during pregnancy suggesting elevated, not reduced nephrogenous cGMP production. Another potential, intriguing mechanism for volume retention during pregnancy relates to renal interstitial hydrostatic pressure (RIHP). Natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) are associated with increases in RIHP. RIHP is reduced at any gven RPP in both midterm and late pregnant rats, which is dictated by an increase in the compliance of the renal capsule and interstitioum. Indeed, one possible chain of events is that there is a primary increase in the compliance of the renal capsule and interstitium during early pregnancy, which reduces RIHP that, in turn, attenuates natriuresis and diuresis, thereby promoting gestational sodium and water retention. This decrease in RIHP may also be abetted by the normal gestational decline in blood pressure. An

increase in renal capsular compliance would also accommodate the 50% increase in renal volume that is observed during normal gestation (at least in women-vide supra). In light of relaxins role in other maternal cardiovascular and renal adaptation to pregnancy including the increases in arterial compliance (vide supra), and its wellknown matrix-degrading properties, this hormone is a na ttractive candidate molecule for mediating the increase in renal interstitial and capsular compliance during pregnancy.

RENAL PATHOPHYSIOLOGY HYPERTENSIVE DISORDERS OF PREGNANCY Hipertensive disorders of pregnancy consist of a broad spectrum of medical complication