Inhibition of the hypothalamic paraventricular nucleus in spontaneously hypertensive rats dramatically reduces sympathetic vasomotor tone

Hypertension. 2002 Feb;39(2):275-80. doi: 10.1161/hy0202.104272.

Abstract

Experimental evidence indicates that the hypothalamic paraventricular nucleus modulates sympathetic vasomotor tone and blood pressure and that this modulation is altered in some cardiovascular diseases. This study tested the hypothesis that this nucleus exerts a more significant tonic excitatory modulation of basal sympathetic vasomotor activity in spontaneously hypertensive rats. In anesthetized, artificially-ventilated rats, bilateral microinjections of the GABA(A) receptor agonist, muscimol (1 to 1.5 nmoles per side), into the paraventricular nucleus produced a depressor and sympathoinhibitory response that did not recover. When compared with normotensive rats, this response was more marked in spontaneously hypertensive rats, where lumbar sympathetic nerve discharge was reduced by 75 +/- 3% and mean arterial pressure fell from 119 +/- 7 mm Hg to 58 +/- 3 mm Hg. Blockade of excitatory and inhibitory amino acid receptors in the rostral ventrolateral medulla significantly attenuated this response. Microinjections of small volumes (<20 nL) of GABA were used to localize precisely the responsive region of the paraventricular nucleus. Unilateral injections of GABA into the dorsomedial cap of the paraventricular nucleus induced a brisk depressor (decrease of 42 +/- 4 mm Hg), sympathoinhibitory (decrease by 72 +/- 2%), and bradycardic (decrease of 77 +/- 16 bpm) response. The mechanisms underlying the sympathoinhibition after inactivation of the paraventricular nucleus are not elucidated, but evidence discussed suggests the involvement of a supracollicular sympathoinhibitory pathway. The results presented demonstrate that the paraventricular nucleus exerts a powerful, tonic effect on the control of sympathetic vasomotor tone under basal conditions in anesthetized rats and that this is enhanced in spontaneously hypertensive rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Blood Pressure / drug effects
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Heart Rate / drug effects
  • Hypertension / physiopathology*
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / physiopathology
  • Muscimol / pharmacology
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / physiopathology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiopathology
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • GABA Agonists
  • GABA Antagonists
  • Muscimol
  • gamma-Aminobutyric Acid
  • Bicuculline