The diabetes-induced functional and distributional changes of the alpha 1-adrenoceptor of the abdominal aorta and distal mesenteric artery from streptozotocin-induced diabetic rats / 대한마취과학회지

BACKGROUND: The aim of this study was to evaluate the effect of diabetes on the function and distribution of vascular alpha1-adrenoceptors in the abdominal aorta and distal mesenteric artery from streptozotocin (STZ)-induced diabetic rats at the level of the alpha1-adrenoceptor subtypes. METHODS: Diabetes was induced by a single intravenous injection of STZ (60 mg/kg) in 8 week-old male Sprague-Dawley rats (n = 11). Age-matched normal rats (n = 14) were used as a control group. Four weeks after STZ injection, the tilting-induced change of the mean arterial pressure was recorded. The alpha1-adrenoceptor subtypes mediating the contractions of the distal mesenteric artery and abdominal aorta were investigated using the agonist phenylephrine and subtype-selective antagonists that included prazocin, 5-methylurapidil and BMY 7378. The expressions of the alpha1-adrenoceptor subtypes of each artery were examined by immunofluorescence staining using the subtype selective antibodies. RESULTS: The recovery of the mean arterial pressure was delayed after positional change in the diabetic rats. Compared with that of the normal rats, the contractile response to phenylephrine was increased in the abdominal aortas and it was decreased in the distal mesenteric arteries in the diabetic rats. In addition, compared with the normal rats, the fluorescent intensity of all the alpha1-adrenoceptor subtypes was increased in the abdominal aortas and it was decreased in the mesenteric arteries of the diabetic rats. CONCLUSIONS: Diabetes increased the contractility of the abdominal aorta in response to phenylephrine, yet diabetes decreased that of the mesenteric arteries in the STZ-induced diabetic rats. Those results are mainly based on the overall change of the alpha1-adrenoceptor, and not on the change of the specific alpha1-adrenoceptor subtypes.

Gender difference and change of alpha1-adrenoceptors in the distal mesenteric arteries of streptozotocin-induced diabetic rats / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate the gender-related changes in the function and distribution of alpha1-adrenoceptors in the distal mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of alpha1-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 45degrees tilting was recorded. The alpha1-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 alpha1-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 alpha1D-adrenoceptor. In STZ-induced male and female diabetic rats, all alpha1-adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with normal rats. CONCLUSIONS: There was the gender-related functional difference of alpha1-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 alpha1-adrenoceptor.

Effects of Dopamine on the Gonadotropin Releasing Hormone(GnRH) Neurons / 대한내분비학회지

BACKGROUND: The gonadotropin releasing hormone (GnRH) neurons represent the final output cells of the neural network that controls fertility. Dopamine (DA) has been shown to control gonadotropin release in many species. However, the direct membrane effects of DA and the related receptors on GnRH neurons remain poorly understood. The purpose of this study was to investigate the direct actions of DA on GnRH neurons and the related receptors using brain slice electrophysiology. METHODS: Gramicidin-perforated patch clamp recordings were made from the GnRH neurons to examine the direct membrane effects of DA in GnRH-EGFP mut5 mice. RESULTS: DA induced hyperpolarization of the GnRH neurons, which was maintained in the presence of tetrodotoxin (TTX), a Na+ channel blocker, suggesting a direct, rather than indirect, action of DA on GnRH neurons. DA-induced hyperpolarizing effects were blocked by prazosin, an alpah1-adrenergic antagonist, and mimicked by phenylephrine (PE), an alpha1-adrenergic agonist. CONCLUSIONS: These data indicate that DA exerts a direct inhibitory effect on GnRH neurons via the alpha1- adrenergic receptors. These results support the general concept that dopaminergic afference represents a predominantly inhibitory component of the GnRH neuronal network.

Activation of Na~+/H~+ exchange 1 and myocardial hypertrophy / 中国药理学通报

Na +/H + exchanger 1 (NHE1) is a major contributor to ischemic and reperfusion injury. It is emerging that NHE 1 also contributes to myocardial hypertrophy and heart failure due to chronic maladaptive stimulation. It appears that NHE 1 may represent a common downstream mediator for various hypertrophic factor, such as angiotensinⅡ,beta (1) and alpha (1) adrenergic receptor activation. NHE 1 inhibition may be a effective new therapeutic approach for prevention and treatment of heart failure.-