Cell and molecular studies of renin secretion.
Renin secretion has been studied in the past at the level of the whole kidney, but the control of the genetic basis of renin synthesis is poorly understood. We have studied the regulation of renin gene expression in the fetus and also in the adult rat in response to angiotensin converting enzyme (ACE) inhibition with enalapril in the presence and absence of angiotensin II (AII). In the fetus, vascular smooth muscle cells of the renal afferent arteriole and feeder vessels contain renin mRNA and immunostain for renin. With maturation, these vessels progressively lose the capacity to synthesize renin, and only the juxtaglomerular cells retain this capacity in the adult. However, in response to ACE inhibition, the adult renal feeder vessels acquire the capacity to synthesize and secrete renin within 7 days. This effect is partially reversed with co-administration of AII. In order to study renin biosynthesis and secretion at the cellular level, we have developed a new method of study of individual renin-secreting cells, the reverse hemolytic plaque assay (RHPA). Utilizing this method, we have demonstrated that ACE inhibition with enalapril increases the number of renin secreting cells by over 15-fold at physiologic calcium concentrations. Enalapril also induced a 3-fold increase in the amount of renin released as estimated by the area of the hemolytic plaques formed. Transmission electron microscopy (EM) of the renin-secreting cell at the center of a hemolytic plaque demonstrates modified vascular smooth muscle cells with cytoplasmic granules. In summary, ACE inhibition stimulates renin mRNA accumulation and redistributes renal renin content toward that observed in early fetal life. AII inhibits renal renin mRNA accumulation. ACE inhibition increases the number of renin secreting cells as well as the amount of renin secreted by each cell. The individual renin secreting cell is a modified vascular smooth muscle cell with cytoplasmic secretory granules. Further studies of the cellular pathways for renin secretion can be provided by EM immunocytochemistry of the individual renin secreting cell.
Ice
K S
KS
University of Virginia School of Medicine, Charlottesville 22908.
Geary
K M
KM
Gomez
R A
RA
Johns
D W
DW
Peach
M J
MJ
Carey
R M
RM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D004656:Enalapril / Q000494:pharmacology; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000235:genetics / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D012083:Renin