1 Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the a 1 -adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2 Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg kg À1 i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3 In the nondiabetic SHR group, mean arterial pressure (MAP) was 14676 mmHg, RBF was 28.071.4 ml min À1 kg À1 and blood glucose was 112.374.7 mg dl À1, and in the diabetic SHR Group, MAP was 14473 mmHg, RBF 26.971.3 ml À1 min kg À1 and blood glucose 316.2710.5 mg dl À1. Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all Po0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all Po0.05) in both the SHR and diabetic SHR. 4 These findings suggest that a 1A and a 1D -adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, a 1B -, and/or a 2 -subtypes.
Aim: This study investigates the subtypes of the α 1 -adrenoceptor mediating the adrenergically-induced renal vasoconstrictor responses in streptozotocin-induced diabetic and non-diabetic 2-kidney one clip (2K1C) Goldblatt hypertensive rats. Methods:The renal blood flow responses to renal nerve stimulation, noradrenaline, phenylephrine, and methoxamine were measured in the absence and presence of nitrendipine, 5-methylurapidil, chloroethylclonidine and BMY 7378. Results: The renal vasoconstrictor responses were markedly attenuated by nitrendipine and 5-methylurapidil in the diabetic rats (all P<0.05). In the non-diabetic rats, these responses were markedly attenuated by nitrendipine, 5-methylurapidil, and BMY 7378 (all P<0.05). In both experimental groups, chloroethylclonidine markedly accentuated the renal vasoconstrictions caused by all the adrenergic stimuli (all P<0.05). Conclusion: These observations indicate that α 1A -adrenoceptor subtypes play a major role in mediating adrenergically-induced renal vasoconstriction in the diabetic 2K1C Goldblatt hypertensive rats. In the non-diabetic 2K1C Goldblatt hypertensive rats, contributions of α 1A and α 1D -adrenoceptor subtypes were proposed. Apart from post-synaptic α 1 -adrenoceptors, both in the diabetic and non-diabetic 2K1C Goldblatt hypertensive rats, the potential involvement of presynaptic α 1 -adrenoceptors is also suggested. Key words
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