Biomechanical coupling in renin-releasing cells.
The renin-angiotensin system is a major regulatory system controlling extracellular fluid volume and blood pressure. The rate-limiting enzyme in this hormonal cascade is renin, which is synthesized and secreted into the circulation by renal juxtaglomerular (JG) cells. The renal baroreceptor is a key physiologic regulator of renin secretion, whereby a change in renal perfusion pressure is sensed by these cells and results in a change in renin release. However, the mechanism, direct or indirect, underlying pressure transduction is unknown. We studied the direct application of mechanical stretch to rat JG cells and human renin-expressing (CaLu-6) cells on the release of renin. JG cells released a low level of baseline renin, comprising < 5% of their total renin content. By contrast, renin secretion from CaLu-6 cells comprised approximately 30% of cellular stores, yet was also stimulated twofold by 10 microM forskolin (P </= 0.001). In JG cells, mechanical stretch inhibited basal renin release by 42% (P < 0.01) and forskolin-stimulated renin release by 25% (P < 0.05). In CaLu-6 cells, stretch inhibited basal- and forskolin-stimulated renin release by 30 and 26%, respectively (both P < 0.01). Northern blot analysis demonstrated a stretch-induced reduction in baseline renin mRNA accumulation of 26% (P < 0.05) in JG and 46% (P < 0.05) in CaLu-6 cells. The data demonstrate that mechanical stretch in renin-releasing cells inhibits basal and stimulated renin release accompanied by a decrease in renin mRNA accumulation. Further studies will be necessary to characterize the intracellular events mediating biomechanical coupling in renin-expressing cells and the relationship of this signaling pathway to the in vivo baroreceptor control of renin secretion.
Carey
R M
RM
Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
McGrath
H E
HE
Pentz
E S
ES
Gomez
R A
RA
Barrett
P Q
PQ
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D012333:RNA, Messenger; D005576:Colforsin; D012083:Renin; D007545:Isoproterenol