title: Telmisartan exerts sustained blood pressure control and reduces blood pressure variability in metabolic syndrome by inhibiting sympathetic activity.
abstract: BACKGROUND
  Accumulating evidence on blood pressure (BP) reduction with various angiotensin II receptor blockers (ARBs) show that the magnitudes and durations of BP control differ across ARBs. However, the mechanism of ARBs is unknown. This work was undertaken to compare telmisartan and valsartan in duration of BP control, BP variability, and effects on the autonomic nervous system.
  
  
  METHODS
  Using radiotelemetry combined with spectral analysis with a fast Fourier transformation algorithm, we compared the effects of various doses of telmisartan and valsartan on BP and its variability during dark (active phase) and light (inactive phase) periods over 5 weeks in SHR/NDmcr-cp(+/+)(SHRcp) rats, a model of metabolic syndrome. We also compared the effects of these ARBs on autonomic nervous system, central oxidative stress, and inflammation in SHRcp rats.
  
  
  RESULTS
  Telmisartan exerted a longer-lasting BP-lowering effect and greater attenuation of BP variability in SHRcp than valsartan. Telmisartan decreased low frequency power of systolic BP and increased spontaneous baroreflex gain in SHRcp during both the dark and light periods more than valsartan. Telmisartan reduced 24-hour urinary norepinephrine excretion more than valsartan. Furthermore, telmisartan attenuated oxidative stress and the numbers of gp91(phox)-positive cells and activated microglia and astrocytes in the rostral ventrolateral medulla of SHRcp rats more than valsartan.
  
  
  CONCLUSIONS
  The superiority of telmisartan over valsartan in sustained BP control and reduction of BP variability was attributed to more suppression of sympathetic activity and more improvement of baroreceptor reflex. The greater suppression of sympathetic activity by telmisartan appeared to be partially mediated by a stronger amelioration of central oxidative stress.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sueta
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Koibuchi
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Yu
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Kensuke
authors.initials: K
authors.lastname: Toyama
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Ken
authors.initials: K
authors.lastname: Uekawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: MingJie
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; mitsuyam@gpo.kumamoto-u.ac.jp.
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D001795:Blood Pressure Determination / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D004867:Equipment Design; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry / Q000295:instrumentation; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan
keywords: angiotensin receptor blocker; blood pressure; blood pressure variability; hypertension; oxidative stress; sympathetic activity; telemetry.