Mechanism for low renin in blacks: studies in hypophysectomised rat model

Black people have a lower plasma renin activity (PRA) than is appropriate for the level of blood pressure, but the mechanism remains unknown. Studies in our laboratory, using the hypophysectomised (Hypox) rat model, have provided a partial explanation of the inappropriately low PRA with respect to BP. Kidneys were isolated and perfused and renin secretion responsiveness studied with isoproterenol (Iso) infusion, calcium (Ca) depletion, and pressure reduction; an enriched preparation of juxtaglomerular (JG) cells was prepared for determination of cellular renin content (CRC); and preparations of isolated renin granules (IRG) and plasma membrane vesicles (PMV) from the purified JG cells were used to assess the storage and compartmentalisation of renin. Renin secretion was lower in Hypox than in normal and sodium (Na) deprived rats. On the other hand, CRC, IRG, and PMV were identical (statistically) in Hypox and Na deprived rats. Despite identical content and storage, kidneys from Hypox rats secreted significantly less renin in response to Iso, Ca depletion, and low pressure. One interesting observation is that upon stimulation, PMV of Hypox rats stored a much larger percentage of renin than normal or Na deprived rats, suggesting that the PMV may play a role as a renin sink in the low PRA levels observed in the Hypox rats. Since black people have renin profiles and responsiveness similar to those in Hypox rats, this model may be useful in studying the mechanisms responsible for their lower PRA.