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RESEARCH ARTICLE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
26
VOLUME 14 NUMBER 1 • JULY 2017
pioglitazone and/or losartan, Clo induced relaxation in the control
aortic rings (Fig. 5).
In the HT group, Clo did not cause relaxation. The contractile
response to Clo was decreased in the presence of pioglitazone and/
or losartan (Fig. 6). In the DM group, the contractile response to
Clo was significantly decreased in the presence of pioglitazone and
losartan, but not in the presence of either pioglitazone or losartan
alone (Fig. 7). In the HT + DM group, the decrease in contractile
response to Clo was not significant in the presence of pioglitazone
and losartan (Fig. 8).
Discussion
This study investigated the effects of pioglitazone and losartan
on aortic contractile responses to alpha adrenoceptors in diabetic
and/or hypertensive rats. We examined the effects of pioglitazone
and losartan on vascular contractility in control, L-NAME-induced
hypertensive, STZ-induced diabetic, and hypertensive diabetic rats.
The major findings of this study were that pre-treatment of rat aortic
rings with pioglitazone (10 µM) and/or losartan (10 µM) decreased
the sensitivity of the contractile responses to phenylephrine and
decreased the maximum clonidine contraction.
Various authors have reported on the blood pressure- lowering
effects of PPAR-gamma agonists such as pioglitazone in rats and
monkeys, and in patients with type 2 diabetes and hypertension.
9,16-18
Majithiya
et al
. noted an increase in SBP in STZ-induced (55 mg/
kg, intravenous) diabetic Sprague-Dawley rats, and also reported
that pioglitazone administration to these rats lowered their blood
pressure.
10
Diep
et al
. showed that treatment with pioglitazone
(10 mg/kg/day) or rosiglitazone (5 mg/kg/day) for seven days
attenuated the development of hypertension, improved endothelial
dysfunction induced by angiotensin II infusion, and corrected
vascular structural abnormalities.
19
Nomura and co-workers reported their findings regarding the
effect of pioglitazone on the contractility of isolated blood vessels.
20
Buchanan and colleagues showed that the addition of pioglitazone
to vascular preparations decreasedKCl- and norepinephrine-induced
vasoconstriction
in vitro
.
11
Accordng to Majithiya and co-workers,
administration of pioglitazone for four weeks restored elevated
blood pressure to normal, reduced the enhanced contractility to
phenylephrine, and restored acetyl choline-induced relaxation.
10
The endothelium is involved in the beneficial vascular action of the
glitazones.
21
Various authors have shown that pioglitazone directly
dilates blood vessels by blocking the calcium channels.
11,22
It has been
reported that a decrease in blood pressure due to pioglitazone is due
to direct dilation of the vascular smooth muscles by blocking the
calcium channels or reducing total peripheral resistance.
11,22,23
In vivo
PPAR-alpha and -gamma agonists have been shown to
reduce superoxide generation, restore endothelial dysfunction and
Figure 1.
Effects of pioglitazone and losartan on the response of aortic segments
to increasing concentrations of phenylephrine in the control group. Cont:
control, Pio: pioglitazone, Los: losartan, Pio+Los: pioglitazone + losartan. Values
are expressed as mean ± SEM.
Figure 2.
Effects of pioglitazone and losartan on the response of aortic segments
to increasing concentrations of phenylephrine in the HT group. Cont: control,
Pio: pioglitazone, Los: losartan, Pio+Los: pioglitazone + losartan. Values are
expressed as mean ± SEM.
Figure 3.
Effects of pioglitazone and losartan on the response of aortic segments
to increasing concentrations of phenylephrine in DM group. Cont: control, Pio:
pioglitazone, Los: losartan, Pio+Los: pioglitazone + losartan. Values are expressed
as mean ± SEM.
Figure 4.
Effects of pioglitazone and losartan on the response of aortic segments
to increasing concentrations of phenylephrine in the HT + DM group. Cont:
control, Pio: pioglitazone, Los : losartan, Pio+Los: pioglitazone + losartan. Values
are expressed as mean ± SEM.