Nitrovasodilators cause endothelium-independent relaxation of blood vessels
by generating nitric oxide (NO). We examined the relaxation and depressor
effects of two organotransition-metal nitrosyl complexes, CpCr(NO)(2)Cl and
CpMo(NO)(2)Cl, relative to those of the prototypal nitrovasodilators, nitr
oglycerin, and sodium nitroprusside (SNP), in phenylephrine-preconstricted
aortic rings and conscious, unrestrained rats. CpCr(NO)(2)Cl, CpMo(NO)(2)Cl
, nitroglycerin and SNP caused dose-dependent relaxation of aortic rings at
maximal responses (E-max) of -118 +/- 4, -113 +/- 4, -104 +/- 1, and -128
+/- 5% and EC50 of 0.14 +/- 0.04, 22 +/- 4, 1.23 +/- 0.65, and 0.063 +/- 0.
013 mu M, respectively. The dose-response curve of CpCr(NO)(2)Cl was displa
ced to the right by hemoglobin, as well as methylene blue, showing involvem
ent of the NO/cGMP pathway. Unlike nitroglycerin, preexposure for 1 h to Cp
Cr(NO)(2)Cl did not alter subsequent relaxation response to the compound, I
ntravenous bolus injections of CpCr(NO)(2)Cl, CpMo(NO)(2)Cl, nitroglycerin,
and SNP caused dose-dependent decreases in MAP with E-max of -42 +/- 2, -5
1 +/- 8, -56 +/- 6, and -58 +/- 2 mm Hg and EC50 of 0.041 +/- 0.010, 13 +/-
4, 1.6 +/- 0.4, and 0.037 +/- 0.004 mu mol/kg, respectively. These results
show that CpCr(NO)(2)Cl and CpMo(NO)(2)Cl are efficacious nitrovasodilator
s in vitro and in vivo.