Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats

Cameron G. McCarthy, Camilla F. Wenceslau, Styliani Goulopoulou, Safia Ogbi, Takayuki Matsumoto, R Clinton Webb

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 (40 mg/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.

Original languageEnglish (US)
Pages (from-to)384-394
Number of pages11
JournalPharmacological Research
Volume113
DOIs
StatePublished - Nov 1 2016

Fingerprint

Chloroquine
Inbred SHR Rats
Blood Pressure
Hypertension
Autoimmunity
Autoimmune Diseases
Cardiovascular Diseases
Therapeutics
Mesenteric Arteries
Inbred WKY Rats
Genetic Models
Antimalarials
Prostaglandin-Endoperoxide Synthases
Intraperitoneal Injections
Antihypertensive Agents
Biological Availability
Acetylcholine
Blood Vessels
Reactive Oxygen Species
Nitric Oxide

Keywords

  • Autoimmunity
  • Chloroquine
  • Endothelial function
  • Hypertension

ASJC Scopus subject areas

  • Pharmacology

Cite this

Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats. / McCarthy, Cameron G.; Wenceslau, Camilla F.; Goulopoulou, Styliani; Ogbi, Safia; Matsumoto, Takayuki; Webb, R Clinton.

In: Pharmacological Research, Vol. 113, 01.11.2016, p. 384-394.

Research output: Contribution to journalArticle

McCarthy, Cameron G. ; Wenceslau, Camilla F. ; Goulopoulou, Styliani ; Ogbi, Safia ; Matsumoto, Takayuki ; Webb, R Clinton. / Autoimmune therapeutic chloroquine lowers blood pressure and improves endothelial function in spontaneously hypertensive rats. In: Pharmacological Research. 2016 ; Vol. 113. pp. 384-394.
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