VASODILATORY PROPERTIES OF RECOMBINANT MAXADILAN

Maxadilan is a peptide from the salivary gland of the sand fly Lutzomy ia longipalpis, a vector for leishmaniasis. Cutaneous injection of fem tomolar quantities of maxadilan produces long-lasting erythema, making it the most potent vasodilator known. Isolated rabbit thoracic and ab dominal aorta, carotid artery, and iliac artery demonstrated dose-depe ndent arterial relaxation in response to maxadilan with a mean effecti ve concentration (EC(50)) of 2.7 +/- 1.5, 2.1 +/- 0.5, 2.6 +/- 0.4, an d 1.9 +/- 0.5 nM, respectively. Maxadilan proved to be at least sevenf old more potent than nitroglycerin in each arterial bed (EC(50) = 25 /- 12, 32 +/- 9, 37 +/- 10, and 22 +/- 13 nM, respectively; P < 0.05 f or each vs. maxadilan). Arterial relaxation to maxadilan was independe nt of endothelium and was equipotent in the thoracic and abdominal aor ta, carotid artery, and iliac artery. Arterial relaxation to maxadilan was not inhibited by K+-channel antagonists, methylene blue, quinacri ne, or ouabain. Maxadilan-mediated arterial relaxation was found to be adenosine 3',5'-cyclic monophosphate (cAMP) dependent, as it was pote ntiated by the phosphodiesterase inhibitors 3-isobutyl-1-methylxanthin e and theophylline, and it was inhibited by the protein kinase A inhib itor H-89. Consistent with this observation, incubation of thoracic ao rta with maxadilan (0.1 mu M) produced a time-dependent increase in ar terial cAMP content coincident with arterial relaxation. Using rabbit aortic smooth muscle cells, we also observed a time-dependent reductio n in intracellular calcium in response to maxadilan. Thus these data i ndicate that maxadilan, a peptide from the sand fly salivary gland, is a potent vasodilator that reduces intracellular calcium through a cAM P-dependent mechanism.