Decreased renal prostaglandin catabolism precedes onset of hypertension in the developing spontaneously hypertensive rat

Abstract

WE have shown in kidneys from normotensive rats, that dramatic age-related changes take place in the catabolism, but not in the biosynthesis, of prostaglandins (PGs)¹. Although PG catabolic enzymes were active in the late prenatal period, they rose to a peak (60-fold relative to the adult) around 19d postnatally, dropping to adult levels by day 40 (ref. 1). We have termed this period of peak activity of PG catabolism the ‘critical prostaglandin period’². Since the PG catabolising system is principally located in the cortex^3,4, and since cortical maturation is almost entirely a postnatal event (during the first 4–5 weeks) supported by an intrarenal blood flow redistribution⁵, the sharp increase in PG catabolism implied an intrinsic requirement by the developing kidney to eliminate locally-formed or plasma PGs. PG catabolism possibly functioned as a protective measure¹ against the potentially harmful effects of the PGs which in this species possess potent vasoconstrictor properties⁶. We theorised that unless inactivated, these compounds could interfere with the redistribution of blood flow to the cortex and consequently with normal corticogenesis. We were therefore interested in investigating the activity of the PG system in spontaneously hypertensive rats (SHR) at various stages of pre- and early hypertension to compare this activity with age-paired groups of control normotensive rats in an attempt to determine first whether an abnormality in the prostaglandin system exists, second, whether this abnormality appears around the ‘critical prostaglandin period’ and, third, whether this abnormality develops before or after the onset of hypertension.