Ca2+ and cyclic adenosine monophosphate involvement in radiographic contrast medium-induced renal vasoconstriction.
OBJECTIVE
To investigate the role of extracellular Ca2+ and cyclic 3'-5' adenosine monophosphate (cAMP), a known second messenger promoting smooth muscle relaxation, in preventing renal vasoconstriction induced by radiographic contrast medium (RCM).


METHODS
Isometric contractions of rabbit renal artery were elicited by potassium chloride and increasing concentrations of meglumine/sodium diatrizoate. To determine the contribution of extracellular Ca2+, nifedipine, a blocker of voltage-dependent L-type Ca2+ channels (VDCC), was applied. The contribution of cAMP was investigated by applying the nonspecific phosphodiesterase (PDE) inhibitors papaverine and theophylline and the specific PDE inhibitor milrinone, all of which prevent degradation of cAMP. Forskolin, an activator of cAMP by stimulating adenylyl cyclase (AC), was also investigated.


RESULTS
RCM elicited contractions that were 24.5% of the KCl control contraction, which was reduced by nifedipine (100 mumol/L) by 34.7%. Papaverine, theophylline, and milrinone inhibited RCM-induced contractions by 69.8%, 64.3%, and 43.7%, respectively. Forskolin reduced the response by 82.2%.


CONCLUSIONS
Ca2+ influx through VDCC partially contributes to RCM-induced renal artery vasoconstriction. Intracellular cAMP appears to be an important second messenger pathway for prevention of this response. These findings emphasize the role of second messenger systems involved in adverse RCM effects and the potential prevention of these effects.
Department of Radiology, Medical College of Wisconsin, Milwaukee 53226, USA.
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Drescher
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D003287:Contrast Media / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D015220:Calcium Channels; D003287:Contrast Media; D014665:Vasodilator Agents; D000242:Cyclic AMP; D009543:Nifedipine; D002118:Calcium