title: Nitric oxide is less effective at inhibiting neointimal hyperplasia in spontaneously hypertensive rats.
abstract: Exogenous administration of nitric oxide (NO) markedly decreases neointimal hyperplasia following arterial injury in several animal models. However, the effect of NO on neointimal hyperplasia in hypertension remains unknown. Here, we employ the spontaneously hypertensive rat (SHR) strain, inbred from Wistar Kyoto (WKY) rats, and the carotid artery balloon injury model to assess the effects of NO on neointimal hyperplasia development. 2weeks after arterial injury, we showed that both rat strains developed similar levels of neointimal hyperplasia, but local administration of NO was less effective at inhibiting neointimal hyperplasia in the SHR compared to WKY rats (58% vs. 79%, P<0.001). Interestingly, local administration of NO did not affect systemic blood pressure in either rat strain. Compared to WKY, the SHR displayed more proliferation in the media and adventitia following balloon injury, as measured by BrdU incorporation. The SHR also showed more inflammation in the adventitia after injury, as well as more vasa vasorum, than WKY rats. NO treatment reduced the vasa vasorum in the SHR but not WKY rats. Finally, while NO decreased both injury-induced proliferation and inflammation in the SHR, it did not return these parameters to levels seen in WKY rats. We conclude that NO is less effective at inhibiting neointimal hyperplasia in the SHR than WKY rats. This may be due to increased scavenging of NO in the SHR, leading to diminished bioavailability of NO. These data will help to develop novel NO-based therapies that will be equally effective in both normotensive and hypertensive patient populations.
authors.affiliation: Division of Vascular Surgery, Northwestern University, Feinberg School of Medicine, United States; Institute for BioNanotechnology, Medicine Northwestern University, Feinberg School of Medicine, United States.
authors.forename: Nick D
authors.initials: ND
authors.lastname: Tsihlis
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Vavra
authors.forename: Janet
authors.initials: J
authors.lastname: Martinez
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Lee
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001973:Bromodeoxyuridine / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000188:drug therapy; D006162:Guanylate Cyclase / Q000032:analysis / Q000187:drug effects; D006965:Hyperplasia / Q000188:drug therapy*; D006973:Hypertension / Q000378:metabolism*; D008264:Macrophages; D058426:Neointima / Q000188:drug therapy*; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D001973:Bromodeoxyuridine
keywords: Balloon injury; Endothelial dysfunction; Hypertension; Neointimal hyperplasia; Nitric oxide; SHR