Research Article
Participation of 5-HT and AT
1
Receptors within
the Rostral Ventrolateral Medulla in the Maintenance of
Hypertension in the Goldblatt 1 Kidney-1 Clip Model
Cássia T. Bergamaschi,
1
Nyam F. Silva,
2
Jose G. Pires,
3,4
Ruy R. Campos,
1
and Henrique A. Futuro Neto
2,3,5
1
Federal University of S˜ ao Paulo, School of Medicine, Rua Botucatu 862, 04023-060 S˜ ao Paulo, SP, Brazil
2
Federal University of Espirito Santo, 29042-751 Vit´ oria, ES, Brazil
3
UNIVIX Medical School, 29075-080 Vit´ oria, ES, Brazil
4
UNESC Medical School, 29703-900 Colatina, ES, Brazil
5
EMESCAM Medical School, 29045-402 Vit´ oria, ES, Brazil
Correspondence should be addressed to Ruy R. Campos; ruy.camposjr@unifesp.br
Received 30 April 2013; Accepted 2 December 2013; Published 21 January 2014
Academic Editor: Claudio Borghi
Copyright © 2014 C´ assia T. Bergamaschi et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Te hypothesis that changes in neurotransmission within the rostral ventrolateral medulla (RVLM) are important to maintain
the high blood pressure (BP) was tested in Goldblatt one kidney-one clip hypertension model (1K-1C). Male Wistar rats were
anesthetized (urethane 1.2 g/kg, i.v.), and the efects of bilateral microinjections into the RVLM of the following drugs were measured
in 1K-1C or control groups: glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid (0.02 mol/L, 100 nL), the angiotensin
AT
1
receptor antagonist candesartan (0.01 mol/L, 100 nL), and the nonselective 5-HT receptor antagonist methiothepin (0.06 mol/L,
100 nL). Experiments in 1K-1C rats were performed 6 weeks afer surgery. In anesthetized rats glutamate response was larger in
hypertensive than in normotensive rats (H: Δ67 ± 6.5; N: Δ43 ± 3.54 mmHg). In contrast, kynurenic acid microinjection into the
RVLM did not cause any change in BP in either group. Te blockade of either AT
1
or 5-HT receptors within the RVLM decreased
BP only in 1K-1C rats. A largest depressor response was caused by 5-HT receptor blockade. Te data suggest that 5-HT and AT
1
receptors act tonically to drive RVLM in 1K-1C rats, and these actions within RVLM contribute to the pathogenesis of this model
of hypertension.
1. Introduction
Te importance of sympathetic nervous system activation
in the pathogenesis of hypertension has been demonstrated,
and the therapeutic value of sympathetic nervous inhibition
in hypertensive patients is already evident and has been
widely studied [1]. Ongoing activity of premotor rostral
ventrolateral medulla (RVLM) neurons is responsible for the
tonic generation of sympathetic vasomotor tone; inhibition of
RVLM neurons causes a large decrease in both arterial blood
pressure (BP) and sympathetic nervous system activity, while
stimulation of this medullary region increases sympathetic
vasomotor outfow and BP [2, 3]. Terefore, changes in the
local neurotransmission within the RVLM can be a mecha-
nism involved in the sympathetic activation in hypertension.
Previous studies demonstrated that microinjection into
the RVLM of excitatory amino acid (EAA) receptor antag-
onists has no efect on basal level of BP [4]. Tis fact has been
interpreted as suggesting that the ongoing RVLM activity
is not dependent on EAA inputs to the RVLM. However,
we showed previously that, in Goldblatt 2-kidneys, one-clip
(2K1C) model, microinjection of kynurenic acid, a broad
spectrum EAA receptor antagonist, into the RVLM, reduced
BP to the same extent as autonomic blockade [5]. Similar
results were later shown in SHR and in Dahl-salt sensitive
rats [6, 7]. On basis of these results, it was proposed that tonic
Hindawi Publishing Corporation
International Journal of Hypertension
Volume 2014, Article ID 723939, 6 pages
http://dx.doi.org/10.1155/2014/723939