Gender difference and change of α(1)-adrenoceptors in the distal mesenteric arteries of streptozotocin-induced diabetic rats

Sang-Hyun Park, Jae-Hyon Bahk, Ah-Young Oh, Nam-Su Gil, Jin Huh, Jong-Hwan Lee, Sang-Hyun Park, Jae-Hyon Bahk, Ah-Young Oh, Nam-Su Gil, Jin Huh, Jong-Hwan Lee

Abstract

Background: The purpose of this study was to evaluate the gender-related changes in the function and distribution of α(1)-adrenoceptors in the distal mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of α(1)-adrenoceptor subtypes.

Methods: Diabetes was induced by intravenous injection of STZ in a dose of 60 mg/kg through the tail vein in 8 week-old male or female Sprague-Dawley rats (n = 13/group). Age-matched normal rats (n = 15) were used as a control group. Four weeks after STZ injection, the change in mean arterial pressure caused by a 45° tilting was recorded. The α(1)-adrenoceptor subtypes mediating contractions of the distal mesenteric artery were investigated using the agonist, phenylephrine as well as subtype-selective antagonists including prazocin, 5-methylurapidil, and BMY 7378. The expression of α(1)-adrenoceptor subtypes of each artery was examined by immunofluorescence staining and western blotting using subtype selective antibodies.

Results: Compared with normal male rats, the contractile response to phenylephrine was decreased in the distal mesenteric artery in normal female rats. Moreover, a decrease in contractile force was observed in STZ-induced diabetic rats compared with age-matched controls. Western blotting revealed that there was the difference between normal male and female rats in manifestation of the α(1D)-adrenoceptor. In STZ-induced male and female diabetic rats, all α(1)-adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with normal rats.

Conclusions: There was the gender-related functional difference of α(1)-adrenoceptors in normal rats. In both male and female rats, diabetes decreased the contractile response in mesenteric arteries, which might be caused by the overall change in α(1)-adrenoceptor.

Keywords: Alpha-1 adrenergic receptor; Gender; Mesenteric arteries; Streptozotocin diabetes.

Figures

Fig. 1
Fig. 1
Time course for the change in mean arterial pressure (MAP) after tilting in normal male (▪), normal female (▴), streptozotocin-induced diabetic male (□) and diabetic female (▵) rats. Each data point represents means ± SD. Data from 13 rats were collected in each group. *P < 0.001 vs. diabetic rats. †P < 0.05 vs. normal rats, ‡P < 0.01 vs. male rats.
Fig. 2
Fig. 2
Hematoxylin and eosin stained images in male (A, B) and female mesenteric arteries (C, D) from normal and streptozotocin-induced diabetic rats. (magnification: ×200). Mesenteric ar ter ies f rom diabet ic rat s were characterized by a decrease in density of muscle fiber at the media of the vessel wall.
Fig. 3
Fig. 3
Immunofluorescence images of the α1A-adrenoceptor subtype in male (A, B) and female mesenteric arteries (C, D) from normal and streptozotocin-induced diabetic rats. (magnification: ×200). Diabetic mesenteric arteries were characterized by a decreased fluorescent intensity.
Fig. 4
Fig. 4
Immunofluorescence images of the α1D-adrenoceptor subtype in male (A, B) and female mesenteric arteries (C, D) from normal and streptozotocin-induced diabetic rats. (magnification: ×200). Diabetic mesenteric arteries were characterized by a decreased fluorescent intensity.
Fig. 5
Fig. 5
(A) A representative Western blot was shown in the top panel and the graphic presentation of alpha 1 - receptors quantified by integrating the volume of autoradiograms from three separate experiments is shown in the bottom panel. (B, C) In diabetic rats, the expressions of the alpha 1A and alpha 1D - receptors were suppressed compared with those in normal rats. (C) The expression of the alpha 1D - receptors was suppressed in female normal rats compared with those in male normal rats. *P < 0.05 vs. male rats. †P < 0.05 vs. normal rats.

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