Key result
Diabetes increases renal artery contractile response to phenylephrine by ~53% in rats.
Why the study?
The contractile responses of renal arteries in diabetic rats compared to controls and the underlying mechanisms involving α1D-adrenoceptor function and Ca2+ transport dysfunction were not fully characterized.
Absolute Event Rate: 1.21% vs 0.79%
In a diabetic rat model, renal arteries demonstrate supersensitivity and hyperreactivity to phenylephrine, suggesting altered α1D-adrenoceptor function and impaired Ca2+ transport.
Hypothesis-generating for enhanced adrenergic reactivity in diabetic renal arteries; human studies needed before clinical relevance.
The Contractile responses of renal artery isolated from streptozotocin (STZ) -induced diabetic rats were compared with those from age-matched control rats. The contraction in renal arteries of the diabetic rats was more sensitive to phenylephrine (PE), and the maximum contraction induced by PE was significantly greater than in controls. The concentration-response to PE was shifted to the right by 10-6 M BMY 7378, a selective α1D-antagonist. In addition, the increased contractile responses to PE after BMY 7378 treatment were still significantly different in diabetics compared to controls at a concentration of greater than 10-6 M PE. The rate of relaxation of the PE-induced contraction was significantly slower in diabetic rats (5.4±0.3 min ) than in controls (3.9±0.4 mm) . Addition of 4.5 mM KCl to K+ -free solution induced relaxation in the presence of 10-5 M PE, which was followed by contraction to about the same level as that before the KCl addition. The duration of KCl-induced relaxation in diabetic rats (19.8±1.1 min) was significantly shorter than that in controls (24.6±1.4 mm) . The contractile response to angiotensin II was greater in renal arteries of diabetic rats than in those from controls. This contraction was facilitated to the same extent in the presence of N-G -nitro-L-arginine, but not significantly. Taken together, these results suggest that the supersensitivity and hyperreactivity to PE in diabetic renal arteries is related to changes in α1D-adrenoceptor function, and to the role of Na+ flow which causes to the dysfunction of Ca2+ transport in diabetic smooth muscle.
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Tajima et al. (2001) studied Streptozotocin-induced diabetes. Streptozotocin (STZ) vs. Citrate-saline buffer (age-matched controls) was evaluated on Maximum contractile response to phenylephrine (PE). The maximum contractile response to phenylephrine was significantly greater in renal arteries from diabetic rats (1.21 g/mg tissue) compared to controls (0.79 g/mg tissue).
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