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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 3, May/June 2016
166
AFRICA
of pioglitazone and/or losartan (Fig 5). In the absence of
pioglitazone and losartan (control), Clo induced contraction.
In the presence of 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
μ
M) and/or losartan (10
μ
M) 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 decreased KCl- 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
-log M Phenylephrine
9
8
7
6
5
4
Contraction (mg)
2000
1500
1000
500
0
Cont
Pio
Los
Pio + Los
Fig. 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.
-log M Phenylephrine
9
8
7
6
5
4
Contraction (mg)
2000
1500
1000
500
0
Cont
Pio
Los
Pio + Los
Fig. 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.
-log M Phenylephrine
9
8
7
6
5
4
Contraction (mg)
2000
1500
1000
500
0
Cont
Pio
Los
Pio + Los
Fig. 3.
Effects of pioglitazone and losartan on the response
of aortic segments to increasing concentrations of
phenylephrine in DM group. Cont: control, Pio: pioglita-
zone, Los: losartan, Pio
+
Los: pioglitazone
+
losartan.
Values are expressed as mean
±
SEM.
-log M Phenylephrine
9
8
7
6
5
4
Contraction (mg)
2000
1500
1000
500
0
Cont
Pio
Los
Pio + Los
Fig. 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.