Effects of hypoxia on renin secretion and renal renin gene expression.
Plasma renin activity (PRA) and renal renin mRNA levels were measured in male rats exposed to hypoxia (8% O2) or to carbon monoxide (CO; 0.1%) for six hours. PRA increased fourfold and 3.3-fold, and renin mRNA levels increased to 220% and 200% of control, respectively. In primary cultures of renal juxtaglomerular (JG) cells, hypoxia (lowering medium O2 from 20% to 3% or 1%) for 6 or 20 hours did not affect renin secretion or gene expression. Renal denervation did not prevent stimulation of the renin system by hypoxia. Because norepinephrine increased 1.7-fold and 3.2-fold and plasma epinephrine increased 3.9-fold and 7.8-fold during hypoxia and CO inhalation, respectively, circulating catecholamines might mediate the stimulatory effects of hypoxia on renin secretion and renin gene expression. Stimulation of beta-adrenergic receptors by continuous infusion of 160 microg/kg/hr isoproterenol increased PRA 17-fold and 20-fold after three and six hours, respectively, and renin mRNA by 130% after six hours. In rats with a stimulated renin system (low-sodium diet), isoproterenol did not stimulate PRA or renal renin mRNA further. In summary, both arterial and venous hypoxia can stimulate renin secretion and renin gene expression powerfully in vivo but not in vitro. These effects seem not to be mediated by renal nerves or by a direct effect on JG cells but might be mediated by circulating catecholamines.
Krämer
B K
BK
Klinik und Poliklinik für Innere Medizin II, Institut für Pharmakologie, Universität Regensburg, Germany.
Ritthaler
T
T
Schweda
F
F
Kees
F
F
Schricker
K
K
Holmer
S R
SR
Kurtz
A
A
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D007606:Juxtaglomerular Apparatus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000235:genetics* / Q000378:metabolism*
D004792:Enzyme Precursors; D012333:RNA, Messenger; D002245:Carbon Dioxide; D012083:Renin; D010100:Oxygen