Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT₁ receptor in the rostral ventrolateral medulla of hypertensive rats

Hypertens Res. 2012 Sep;35(9):940-6. doi: 10.1038/hr.2012.63. Epub 2012 May 10.

Abstract

In patients and animals with hypertension, sympathetic nervous system (SNS) activation is present. We have demonstrated that angiotensin II type 1 receptor (AT₁R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, causes SNS activation in hypertensive rats. The aim of the present study was to determine whether orally administered AT₁R blockers (ARBs) inhibit SNS activation through an anti-oxidant effect via inhibition of AT₁R in the RVLM of hypertensive rats and, if so, whether the benefits are class effects of ARBs. Stroke-prone spontaneously hypertensive rats (SHRSPs), a hypertensive model with sympathoexcitation, were divided into four groups: SHRSPs treated with telmisartan (TLM), candesartan (CAN), or hydralazine (HYD) and a vehicle group (VEH). Although systolic blood pressure was reduced in the TLM, CAN and HYD groups to the same level, heart rate, SNS activation and oxidative stress in the RVLM were significantly lower in the TLM group only. The pressor effect caused by the microinjection of angiotensin II into the RVLM and the depressor effect caused by the microinjection of tempol, a superoxide dismutase mimetic, into the RVLM were both significantly smaller in TLM, but not in CAN or HYD. These results suggest that orally administered TLM inhibits SNS activation through an anti-oxidant effect via inhibition of AT₁R in the RVLM of SHRSPs; these results are also independent of depressor effects and are not class effects of ARBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / administration & dosage
  • Acetophenones / pharmacology
  • Administration, Oral
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / pharmacology*
  • Benzoates / administration & dosage
  • Benzoates / pharmacology*
  • Blood Pressure / drug effects
  • Cyclic N-Oxides / administration & dosage
  • Cyclic N-Oxides / pharmacology
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Heart Rate / drug effects
  • Hydralazine / pharmacology
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Medulla Oblongata / drug effects*
  • Microinjections
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism
  • Norepinephrine / urine
  • Rats
  • Rats, Inbred SHR
  • Receptor, Angiotensin, Type 1 / drug effects*
  • Spin Labels
  • Sympathetic Nervous System / drug effects*
  • Sympatholytics*
  • Telmisartan
  • Tetrazoles / pharmacology
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Acetophenones
  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Benzimidazoles
  • Benzoates
  • Cyclic N-Oxides
  • Enzyme Inhibitors
  • Receptor, Angiotensin, Type 1
  • Spin Labels
  • Sympatholytics
  • Tetrazoles
  • Thiobarbituric Acid Reactive Substances
  • Hydralazine
  • acetovanillone
  • NADPH Oxidases
  • candesartan
  • Telmisartan
  • tempol
  • Norepinephrine