CD59 or C3 are not requred for angiotensin II-dependent hypertension or hypertrophy in mice.

Complement is a major pro-inflammatory innate immune system whose serum activity correlates with systolic blood pressure in humans. To date, no studies using in vivo models have directly examined the role of individual complement components in regulating vessel function, hypertension and cardiac hypertrophy. Herein, in vivo responses to angiotensin (ang) II were characterized in mice deficient in CD59a or C3. CD59a(-/-) mice had slightly but significantly elevated systolic blood pressure (107.2 +/- 1.7 mmHg versus 113.8 +/- 1.31 mmHg, P < 0.01, for wild-type and CD59a(-/-), respectively). Aortic rings from CD59a(-/-) mice showed significantly less platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, with elevated deposition of membrane attack complex. However, acetylcholine- and sodium nitroprusside-dependent dilatation, plasma nitrate/nitrite and aortic cyclic guanosine monophosphate levels were unchanged from wild-type. Also, in vivo infusion with either ang II or noradrenaline caused similar hypertension and vascular hypertrophy to wild-type. Mice deficient in C3 had similar basal blood pressure to wild type and showed no differences in hypertension or hypertrophy responses to in vivo infusion with ang II. These data indicate that CD59a deficiency is associated with some vascular alterations that may represent early damage occurring as a result of increased complement attack. However, a direct role for CD59a or C3 in modulating development of ang II-dependent hypertension or hypertrophy in vivo is excluded and we suggest caution in development of complement intervention strategies for hypertension and heart failure.