cGMP and atrial natriuretic factor regulate cell volume of rabbit atrial myocytes.
Atrial natriuretic factor (ANF) reduces the volume of atrial myocytes by inhibiting Na+/K+/2Cl- cotransport. We determined the role of cGMP and cAMP in ANF-induced shrinkage by using digital video microscopy to measure cell volume; volumes are reported relative to control. ANF (1 mumol/L) reversibly reduced atrial cell volume from 1.0 to 0.915 +/- 0.005 (mean +/- SEM). This effect was mimicked by 10 mumol/L 8-bromo-cGMP (8-Br-cGMP), which decreased myocyte volume to 0.894 +/- 0.007 with an ED50 of 0.99 +/- 0.05 mumol/L. In contrast, 100 mumol/L 8-bromo-cAMP (8-Br-cAMP) did not affect volume, and activating the cAMP pathway with 100 mumol/L 8-Br-cAMP did not alter the volume decrease caused by 8-Br-cGMP or ANF. Inhibition of Na+/K+/2Cl- cotransport with bumetanide (1 mumol/L) also reduced cell volume and prevented further shrinkage on subsequent exposure to 8-Br-cGMP. Similarly, 8-Br-cGMP (10 mumol/L) prevented further shrinkage by ANF. Block of Na(+)-H+ exchange, a participant in volume regulation in other cells, did not alter the response to 8-Br-cGMP. More evidence implicating cGMP was obtained by altering its metabolism. LY83583 (10 mumol/L), a guanylate cyclase inhibitor, blocked ANF-induced cell shrinkage. Zaprinast (100 mumol/L), a cGMP-specific phosphodiesterase inhibitor, markedly potentiated the effect of a threshold concentration of ANF (0.01 mumol/L). The actions of ANF, LY83583, and zaprinast on cGMP levels were verified by radioimmunoassay. These data strongly support the idea that the cGMP cascade is the intracellular signaling pathway responsible for ANF-induced atrial cell shrinkage.(ABSTRACT TRUNCATED AT 250 WORDS)
Clemo
H F
HF
Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Baumgarten
C M
CM
D000818:Animals; D016275:Atrial Function; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002469:Cell Separation; D048429:Cell Size / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D006325:Heart Atria / Q000166:cytology*; D017136:Ion Transport / Q000187:drug effects; D018715:Microscopy, Video; D011817:Rabbits; D015290:Second Messenger Systems / Q000502:physiology
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP