Angiotensin Type 1 Receptors and Superoxide Anion Production in Hypothalamic Paraventricular Nucleus Contribute to Capsaicin-Induced Excitatory Renal Reflex and Sympathetic Activation

Neurosci Bull. 2020 May;36(5):463-474. doi: 10.1007/s12264-019-00460-y. Epub 2020 Jan 27.

Abstract

Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.

Keywords: Angiotensin; Blood pressure; Paraventricular nucleus; Reactive oxygen species; Renal reflex; Sympathetic activity.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Acetophenones / pharmacology
  • Acetylcysteine / pharmacology
  • Allopurinol / pharmacology
  • Angiotensin II / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Blood Pressure / physiology
  • Capsaicin / pharmacology*
  • Captopril / pharmacology
  • Ditiocarb / pharmacology
  • Kidney / drug effects*
  • Kidney / innervation
  • Kidney / physiology
  • Losartan / pharmacology
  • Male
  • NADPH Oxidases / antagonists & inhibitors
  • Onium Compounds / pharmacology
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1
  • Reflex / drug effects*
  • Reflex / physiology
  • Superoxides / metabolism*

Substances

  • Acetophenones
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Onium Compounds
  • Receptor, Angiotensin, Type 1
  • Superoxides
  • Angiotensin II
  • Allopurinol
  • diphenyleneiodonium
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Ditiocarb
  • Captopril
  • acetovanillone
  • NADPH Oxidases
  • Losartan
  • Capsaicin
  • Acetylcysteine