title: Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure.
abstract: Our previous study demonstrated a contribution of the paraventricular nucleus (PVN) of the hypothalamus in the processing of the carotid body (CB) chemoreflex. Nitric oxide (NO) (within the PVN), known to modulate autonomic function, is altered in rats with heart failure (HF). Therefore, the goal of the present study was to examine the influence of endogenous and exogenous NO within the PVN on the sympathoexcitatory component of the peripheral chemoreflex in normal and HF states. We measured mean arterial blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) in sham-operated and HF rats (6-8 wk after coronary artery ligation) after incremental doses of potassium cyanide (25-100 mug/kg iv). There was potentiation of the reflex responses in HF compared with sham-operated rats. Bilateral microinjection of an inhibitor of NO synthase, N(G)-monomethyl-l-arginine (50 pmol), into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation in sham-operated rats but had no effect in HF rats. Conversely, bilateral microinjection of a NO donor, sodium nitroprusside (50 nmol), into the PVN attenuated the RSNA response of the peripheral chemoreflex in sham-operated rats but to a smaller extent in HF rats. These data indicate that 1) NO within the PVN plays an important role in the processing of the CB chemoreflex and 2) there is an impairment of the NO function within the PVN of HF rats, which contributes to an augmented peripheral chemoreflex and subsequent elevation of sympathetic activity in HF.
authors.affiliation: Dept. of Cellular & Integrative Physiology, Univ. of Nebraska College of Medicine, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.
authors.forename: Maram K
authors.initials: MK
authors.lastname: Reddy
authors.forename: Harold D
authors.initials: HD
authors.lastname: Schultz
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Kaushik P
authors.initials: KP
authors.lastname: Patel
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001794:Blood Pressure; D002344:Carotid Body / Q000503:physiopathology*; D002628:Chemoreceptor Cells / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010791:Phrenic Nerve / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex
chemical_list: D009569:Nitric Oxide