Sustained hypertension increases the density of AMPA receptor subunit, GluR1, in baroreceptive regions of the nucleus tractus solitarii of the rat.
AMPA-type glutamate receptors in the nucleus tractus solitarii (NTS) are necessary for the baroreceptor reflex, a primary mechanism for homeostatic regulation of blood pressure. Within NTS, the GluR1 subunit of the AMPA receptor is found primarily in dendritic spines. We previously showed that both GluR1 and dendritic spine density are increased in NTS of spontaneously hypertensive rats (SHRs). We hypothesize that both receptor and synaptic plasticity are induced by a sustained elevation in arterial pressure. To test the general nature of this hypothesis, we examined whether similar changes in GluR1 density are found in a renovascular model of hypertension, the DOCA-salt rat, and if these changes are preventable by normalizing blood pressure with hydralazine, a peripherally acting vasodilator. Using immunoperoxidase detection, GluR1 appears as small puncta at the light microscopic level, and is found in dendritic spines at the ultrastructural level. Following the development of hypertension, GluR1 spine and puncta counts were significantly greater in DOCA-salt rats than controls. Hydralazine treatment (4-5 weeks) prevented the development of hypertension in DOCA-salt rats and reduced blood pressure of SHRs to normotensive levels. The density of GluR1 puncta in the NTS was significantly reduced by hydralazine treatment in the SHR model. These results show that hypertension alters dendritic spines containing AMPA-type glutamate receptors within NTS, suggesting that adjustments in GluR1 expression within NTS are part of the synaptic adaptations to the hypertensive state.
Hermes
Sam M
SM
Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Mitchell
Jennifer L
JL
Silverman
Marc B
MB
Lynch
Patrick J
PJ
McKee
Brenda L
BL
Bailey
Timothy W
TW
Andresen
Michael C
MC
Aicher
Sue A
SA
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016253:Microscopy, Immunoelectron; D009924:Organ Culture Techniques; D011311:Pressoreceptors / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014665:Vasodilator Agents / Q000494:pharmacology; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D018698:Glutamic Acid; D006830:Hydralazine; D018091:Receptors, AMPA; D014665:Vasodilator Agents