Treatment with the anabolic steroid, nandrolone, reduces vasoconstrictor responses in rabbit arteries

The objective of this study was to analyze the effect of chronic treatment of rabbits for 4, 8 and 12 weeks with the anabolic steroid, nandrolone, on the contractile responses induced by different agents in segments of thoracic aorta and mesenteric and femoral arteries. In the three types of arteries, the contractions elicited by noradrenaline, 5-hydroxytryptamine and angiotensin II were increased by endothelium removal. The treatment reduced the contractions elicited by the three agents (mainly those caused by 5-hydroxytryptamine) in aorta, and only those caused by 5-hydroxytryptamine in mesenteric arteries. Ca(2+)-free medium containing 0.1 mM ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) reduced the responses elicited by 1 microM noradrenaline, 10 microM 5-hydroxytryptamine and 0.1 microM angiotensin II in aorta segments from control rabbits. Addition of CaCl2 to this medium restored the initial responses elicited by the three agents in normal medium, both in arteries from control and treated rabbits. In aorta, the contractions elicited by phorbol 12,13-dibutyrate (PDB), an activator of protein kinase C, were reduced by the treatment. Staurosporine, an inhibitor of protein kinase C, reduced the responses evoked by PDB. Likewise, the contractions caused by noradrenaline, 5-hydroxytryptamine and especially by angiotensin II were also reduced by staurosporine. These results suggest that the thoracic aorta is the most affected by the treatment, and that the reduction of contractile responses appears to be due to changes in protein kinase C activity and/or in a mechanism situated beyond protein kinase C activation.