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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016
168
AFRICA
In our study, we suggest that our diabetic rats did not have
enough time to develop a sufficiently severe degree of vascular
dysfunction to manifest an effect to phenylephrine. From
our results, acute pioglitazone/losartan pre-treatment did not
significantly change the maximum contractile responses to
phenylephrine in the control, diabetic or hypertensive rats.
We attempted to determine whether these drugs affected the
endothelial modulatory responses to vasoconstriction produced
by phenylephrine. Sensitivity of the aortic rings to phenylephrine
was decreased in the presence of pioglitazone and/or losartan.
The glitazones have been shown by Asano
et al
. to decrease
smooth muscle cell contractility,
34
and by Dormandy
et al.
to
cause improvement in vascular function.
35
We believe, however,
that the blunted adrenergic responses observed in the presence
of glitazones were mediated by the action of these drugs
on the endothelial cells, since the effect disappeared when
the endothelium was removed in a study Mendizabal and
co-workers.
21
Conclusion
In this study,
in vitro
experiments were carried out to investigate
the direct effect of pioglitazone and/or losartan on aortic rings
of control, diabetic, hypertensive and hypertensive diabetic
rats. Our results demonstrate that vascular sensitivity to an
alpha adrenoceptor agonist was decreased in the presence of
pioglitazone and/or losartan in diabetic and/or hypertensive
rat aortic rings. We postulate that these results explain at least
in part the beneficial effects of pioglitazone and losartan
for hypertension and diabetes. The mechanism of action of
pioglitazone and losartan to improve vascular reactivity may
be as a result of intracellular protection from oxygen free
radicals. Our findings suggest a possible beneficial combination
of thiazolidinediones and angiotensin receptor blockers for
treatment of diabetes and hypertension.
Further studies are required to elucidate the effects of
pioglitazone and losartan on alpha receptors and on the
mediators of NO metabolism. It is also remains unclear how
pioglitazone and losartan inhibited alpha-2 receptor activities
in our rat aortic rings. Further investigation is needed to clarify
these underlying mechanisms.
This study was supported by research funding from ADU (TPF09019). We
thank Santek Medikal (Izmir, Turkey) for generously donating the IME-DC
®
Glucometer (GmbH, Germany) and Sandoz (Istanbul, Turkey) for the piogl-
itazone.
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