title: Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats.
abstract: It has been suggested that hypertension results from a loss of immunological tolerance and the resulting autoimmunity may be an important underlying factor of its pathogenesis. This stems from the observations that many of the features involved in autoimmunity are also implicated in hypertension. Furthermore, the underlying presence of hypertension and cardiovascular disease are frequently observed in patients with autoimmune diseases. Antimalarial agents such as chloroquine are generally among the first line treatment options for patients with autoimmune diseases; however, whether they can improve a hypertensive phenotype in a genetic model of essential hypertension remains to be clarified. Therefore, we hypothesized that chloroquine treatment would improve endothelial function and lower blood pressure in spontaneously hypertensive rats (SHR). We treated adult SHR and Wistar-Kyoto rats (12 weeks old), as well as a group of young SHR (5 weeks old), with chloroquine (40mg/kg/day via intraperitoneal injection) for 21 days. Chloroquine lowered blood pressure in adult SHR, but did not impede the development of high blood pressure in young SHR. In isolated mesenteric resistance arteries from SHR of both ages, chloroquine treatment inhibited cyclooxygenase-dependent contraction to acetylcholine, lowered vascular and systemic generation of reactive oxygen species, and improved nitric oxide bioavailability. Overall, these data reveal the anti-hypertensive mechanisms of chloroquine in the vasculature, which may be important for lowering risk of cardiovascular disease in patients with autoimmune diseases. Furthermore, it adds to the growing body of evidence suggesting that autoimmunity underlies hypertension.
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA. Electronic address: cmccarthy@augusta.edu.
authors.forename: Cameron G
authors.initials: CG
authors.lastname: McCarthy
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA.
authors.forename: Camilla F
authors.initials: CF
authors.lastname: Wenceslau
authors.affiliation: Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Styliani
authors.initials: S
authors.lastname: Goulopoulou
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA.
authors.forename: Safia
authors.initials: S
authors.lastname: Ogbi
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Physiology, Augusta University, Augusta, GA, USA.
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects*; D002738:Chloroquine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002738:Chloroquine; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine
keywords: Autoimmunity; Chloroquine; Endothelial function; Hypertension