CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 1, January/February 2011
AFRICA
17
rats with an increased tachycardic reflex may be more susceptible
to higher sympathetic nervous activity, since we did not measure
this. Future studies are necessary to explore this possibility.
The currently reported differences in baroreflex sensitivity
between SHRs from the same laboratory might be due to factors
such as spontaneous mutations, genetic contamination of the
breeding stock, or non-genetic influences (e.g. vertically trans-
mitted diseases or differences in the prenatal and neonatal envi-
ronments existing at different breeding facilities).
17
In the article
that describes the initial development of the SHR, Okamoto and
Aoki
18
stated that the rats were selected from a Wistar strain that
had been maintained by inbreeding. Therefore, it is conceivable
that the normotensive Wistar rats sent from Kyoto to the National
Institute of Health (NIH) in 1971 were at least partially inbred.
However, the precise circumstances of the brother–sister mating
are not clear because records from the NIH indicate that: (1) the
SHR were developed from an ‘outbred Wistar Kyoto male’ and
(2) the Wistar rats from Kyoto used by the NIH to breed WKY
were from ‘non-inbred’ stock.
18
In this study baroreflex function was evaluated in conscious
rats, since baroreflex activity is blunted under anesthesia,
19,20
thus
reducing the range of HR, which would impact on the outcome
in an analysis on a restricted portion of the baroreflex response.
Therefore, we believe that this study provides accurate informa-
tion regarding the discrepancy of baroreflex function between
rats of the same strain (in our case the SHR strain). It would also
be interesting to compare other cardiovascular reflexes (such as
the cardiopulmonary reflex and chemoreflex) in other strains of
rat, such as the SHR stroke prone (SHRSP), and in other animals,
such as rabbits and mice.
These data present clinically relevant information, since
the baroreceptor reflex is currently studied mainly in different
models and strains of rats, aiming to prevent hypertension devel-
opment in the human,
11,20,21
due the fact that reduced baroreflex
function is indicative of cardiovascular disease.
22-24
Since SHR
strains are being used extensively throughout the world, research-
ers should be aware of the genealogical background of the SHR.
It was also previously shown that genetic markers of WKY,
such as asylosterase isozyme patterns, differed among the avail-
able strains of WKY (unpublished observation). Such informa-
tion is useful for researchers who are using SHRs in comparison
with WKY, and may assist in understanding the correct usage of
SHRs, as well as the control WKY strain.
Conclusion
We demonstrated a significant variation in the baroreflex sensi-
tivity between SHRs of the same laboratory and we concluded
that this may significantly influence future studies employing the
SHR as research model.
This research was supported by public funding from Fundação de Amparo à
Pesquisa do Estado de São Paulo (FAPESP).
References
1. Frohlich ED. Hypertension 1986. Evaluation and treatment – why and
how.
Postgrad Med
1986;
80
: 28–36, 41–46.
2. Guyenet PG. The sympathetic control of blood pressure.
Nat Rev
Neurosci
2006;
7
: 335–346.
3. Opie LH. Hypertension, the changing pattern of drug usage.
Cardiovasc
J Afr
2009;
20
: 52–56.
4. Seedat YK. Perspectives on research in hypertension.
Cardiovasc J Afr
2009;
20
: 39–42.
5. La Rovere MT, Bersano C, Gnemmi M, Specchia G, Schwartz PJ.
Exercise-induced increase in baroreflex sensitivity predicts improved
prognosis after myocardial infarction
. Circulation
2002;
106
: 945–949.
6. Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O,
et
al
. Arterial baroreflex modulation of heart rate in chronic heart fail-
ure: clinical and hemodynamic correlates and prognostic implications.
Circulation
1997;
96
: 3450–3458.
7. Cai GJ, Miao CY, Xie HH, Lu LH, Su DF. Arterial baroreflex dysfunc-
tion promotes atherosclerosis in rats.
Atherosclerosis
2005;
183
: 41–47.
8. Shu H, Yi-Ming W, Xu LP, Miao CY, Su DF. Increased susceptibility of
ventricular arrhythmia to aconitine in anesthetized rats is attributed to
the inhibition of baroreflex.
Clin Exper Pharmacol Physiol
2004;
31
:
249–253.
9. Kurtz TW, Morris RC Jr. Biological variability in Wistar-Kyoto rats.
Implications for research with the spontaneously hypertensive rat.
Hypertension
1987;
10
: 127-31.
10. Liu AJ, Ling G, Wu J, Shen FM, Wang DS, Lin LL,
et al
. Arterial barore-
flex function is an important determinant of acute cerebral ischemia in
rats with middle cerebral artery occlusion.
Life Sci
2008;
83
: 388–393.
11. Valenti VE, Ferreira C, Meneghini A, Ferreira M, Murad N, Ferreira
Filho C,
et al
. Evaluation of baroreflex function in young spontaneously
hypertensive rats.
Arq Bras Cardiol
2009;
92
: 205–209.
12. Valenti VE, Imaizumi C, Abreu LC, Colombari E, Sato MA, Ferreira C.
Intra-strain variations of baroreflex sensitivity in Young Wistar-Kyoto
rats.
Clin Invest Med
2009;
32
: E251–E257.
13. Gava AL, Peotta VA, Cabral AM, Meyrelles SS, Vasquez EC. Decreased
baroreflex sensitivity in isoproterenol-treated mice with cardiac hyper-
trophy.
Auton Neurosci
2004;
114
: 47–54.
14. Gao XY, Zhang F, Han Y, Wang HJ, Zhang Y, Guo R, Zhu GQ. AT1
receptor in rostral ventrolateral medulla mediating blunted baroreceptor
reflex in spontaneously hypertensive rats.
Acta Pharmacol Sin
2004;
25
:
1433–1438.
15. Lundin S, Ricksten SE, Thoren P. Interaction between mental stress and
baroreceptor control of heart rate and sympathetic activity in conscious
spontaneously hypertensive (SHR) and normotensive (WKY) rats.
J
Hypertens
1983;
1
(Suppl): 68–70.
16. Judy WV, Watanabe AM, Henry DP, Besch HR Jr, Murphy WR, Hockel
GM. Sympathetic nerve activity: role in regulation of blood pressure in
the spontaenously hypertensive rat.
Circ Res
1976;
38
: 21–29.
17. Grisk O, Exner J, Schmidt M, Honig A. Effects of acute hypoxia and
hyperoxia on ventilation in spontaneously hypertensive and normoten-
sive rat.
J Auton Nerv Syst
1996;
57
: 177–180.
18. OkamotoK, Aoki K. Development of a strain of spontaneously hyperten-
sive rats.
Jpn Circ J
1963;
27
: 282–293.
19. Shimokawa A, Kunitake T, Takasaki M, Kannan H. Differential effects
of anesthetics on sympathetic nerve activity and arterial baroreceptor
reflex in chronically instrumented rats.
J Auton Nerv Syst
1998;
72
:
46–54.
20. Fluckiger JP, Sonnay M, Boillat N, Atkinson J. Attenuation of the baro-
receptor reflex by general anesthetic agents in the normotensive rat.
Eur
J Pharmacol
1985;
109
: 105–109.
21. Souza HC, De Araújo JE, Martins-Pinge MC, Cozza IC, Martins-Dias
DP. Nitric oxide synthesis blockade reduced the baroreflex sensitivity in
trained rats.
Auton Neurosci
2009 May 12 (E-pub ahead of print).
22. Goldman RK, Azar AS, Mulvaney JM, Hinojosa-Laborde C, Haywood
JR, Brooks VL. Baroreflex sensitivity varies during the rat estrous cycle:
role of gonadal steroids.
Am J Physiol Regul Integr Comp Physiol
2009;
296
: R1419–1426.
23. Souza HC, Ballejo G, Salgado MC, Da Silva VJ, Salgado HC.
Cardiac sympathetic overactivity and decreased baroreflex sensitivity
in L-NAME hypertensive rats.
Am J Physiol Heart Circ Physiol
2001;
280
: H844–850.
24. Deley G, Picard G, Taylor JA. Arterial baroreflex control of cardiac
vagal outflow in older individuals can be enhanced by aerobic exercise
training.
Hypertension
2009;
53
: 826–832.