Atrial natriuretic factor (ANF) inhibits arginine vasopressin-stimulated Ca2+ fluxes and cell contraction in vascular smooth muscle cells.
Atrial natriuretic factor (ANF) has been shown to be a potent vasodilator in blood vessels preconstricted by a vasopressor. It is, however, still unknown how ANF interferes with the effects of vasoconstrictors at the cellular level. In the present study the effects of ANF on vasopressin-induced Ca2+ fluxes and cell contraction were examined in primary cultures of vascular smooth muscle cells (VSMC) derived from rat aorta. Spontaneous 45Ca uptake was not affected by 10(-8) M ANF. However, ANF blocked the AVP (10(-8) M)-stimulated 45Ca uptake completely (13.04 +/- 1.42 vs 9.80 +/- 0.46 X 10(3) cpm/mg prot, p less than 0.05). ANF also did not change spontaneous 45Ca efflux from VSMC, whereas it inhibited stimulation of 45Ca efflux by AVP that can be observed within 30 sec (2.59 +/- 0.37 vs 1.39 +/- 0.10 X 10(3) cpm/mg prot/30 sec, p less than 0.01). AVP-induced cell contraction could be prevented by previous incubation with 10(-8) M ANF. ANF stimulated production of cyclic guanosine monophosphate (cGMP) in a dose dependent manner from 10(-9) to 10(-6) M. The stable nucleotide analogue 8-bromo cGMP (1 mM) significantly reduced AVP-stimulated 45Ca efflux (p less than 0.05) and 45Ca uptake (p less than 0.05). Ca fluxes and cell contraction were studied in the presence of 10(-4) M methylene blue (MB) which inhibits soluble guanylate cyclase. MB did not affect the inhibitory effects of ANF on AVP-stimulated 45Ca uptake and efflux. In the presence of MB ANF still blocked AVP-induced cell contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D001127:Arginine Vasopressin; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D002118:Calcium; D008751:Methylene Blue