Disparate effects of captopril on hypertension and blood vessel

Aim: To study whether the effect of captopril (Cap) on vascular structure and function may be separated from its effect on blood pressure. Methods: Captopril treatment (group Cap A and B, 20 and 100 mg �� kg -1 �� d -1) was given to SHR rats during pregnancy, weaning, and up to 16 wk of age. Study performed at 40 wk. Blood pressure (BP) was measured by tail-cuff sphygmomanometer, and wall/lumen ratio of mesenteric artery 3rd grade branch was assessed by morphometric assay. Resistance vessel properties were determined by hindquarter perfusion pressure responses to incremental doses of phenylephrine, in the presence of N(��) nitro-L-arginine methyl ester (L-NAME) or the L-arginine, the precursor of nitric oxide synthesis. Results: Both doses of Cap prevented hypertrophy of blood vessels to an extent comparable to that of the untreated WKY rats (wall/lumen ratio of mesenteric artery, Cap A: 0.38 �� 0.08, Cap B: 0.29 �� 0.05 vs WKY: 0.34 �� 0.11, P > 0.05, respectively). The parameters derived from hindquarter perfusion pressure curves in Cap treated group were almost identical to that of WKY, significantly different from that of untreated SHR (EC 50, Cap B 4.05 �� 2.58 vs SHR 1.15 �� 0.96 mL �� L -1, P < 0.01; vs WKY 5.13 �� 1.97 mL �� L -1, P > 0.05). Addition of L-NAME or L-arginine in the perfusate augmented or attenuated the vasoconstriction responses in the Cap treated group. Conclusion: Cap initiated from intrauterine period normalized the vascular structure and vasoconstrictive responses in SHR when BP still sustained at a higher level vs WKY.