Stroke related alterations in the modulation of cerebrovascular pressure dependent constriction (PDC) by nitric oxide synthases (NOS) in stroke prone spontaneously hypertensive rats (SHRsp)

Abstract

We studied the modulation of PDC by NOS in middle cerebral arteries (MCAs) of SHRsp in relation to hemorrhagic stroke (HS) using a pressure myograph. Confocal microscopy indicated endothelial and neuronal NOS (eNOS, nNOS) in the endotheliumn, nNOS and inducible NOS (iNOS) in the smooth muscle and nNOS in the adventitia of MCAs. In MCAs from prestroke SHRsp, endothelial removal, or the nonspecific NOS inhibitor Nω‐nitro‐L‐arginine methyl ester (LNAME,100µM) shifted PDC to a 100 mmHg pressure step to constricted levels. Endothelial removal did not alter PDC in the presence of LNAME. In de‐endothelialized MCAs, the selective nNOS inhibitor AAAN (10μM, n‐[(4S)‐4‐amino‐5‐[(2‐aminoetheyl)amino]pentyl]‐N‐nitroguanidine) also shifted PDC to more constricted levels. The effects of AAAN could be duplicated but not amplified by LNAME or the NO scavenger hydroxocobalamine (200μM). The iNOS inhibitor 1400W (1.13μM) did not alter tone or PDC. We believe NO generated by endothelial eNOS (and perhaps nNOS) and nonendothelial nNOS (but not iNOS) shifts the operating range of PDC to more dilated diameters in MCAs from prestroke SHRsp. After HS, MCAs from SHRsp could not elicit PDC and were unreactive to LNAME. Reactivity to the NO donor Na‐nitroprusside was unaltered. The MCAs exhibited the presence of eNOS and nNOS, however the latter enzymes appeared to lack the ability to generate NO.