Functional subtypes of renal α₁-adrenoceptor in diabetic and non-diabetic 2K1C Goldblatt renovascular hypertension

Abstract

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

Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar–Kyoto rats

“…In the control rats, our findings were consistent with previously reported data, in that renal vasonstrictor responses elicited by exogenous administration of NA, PE, or ME were blunted in the presence of BMY 7378 in normal rats (Armenia et al 2004(Armenia et al , 2008Khan et al 2008a). These findings suggest that the ␣ 1D -adrenoceptor subtype is contributing to the renal vasoconstriction at the basal level.…”

The Relation between Fructose-Induced Metabolic Syndrome and Altered Renal Haemodynamic and Excretory Function in the Rat

“…In support of this notion, studies from our laboratory have shown that adrenergic- and Ang II-mediated renal vasoconstrictions were attenuated in fructose-fed rats [16] (Figure 2(a)). In addition, using another model of metabolic syndrome, we reported that the streptozotocin-induced diabetic rats had attenuated responses to adrenergic stimulation [144] (Figure 2(b)). One explanation for the reported blunted renal vasoconstrictor responses to Ang II and adrenergic agonists is the higher circulating levels of Ang II and noradrenaline and raised urinary excretion of noradrenaline in fructose-fed rats [112, 113].…”

“…The vascular response to adrenergic stimuli as assessed by reduction in total renal blood flow (RBF) due to renal vasoconstriction was slightly lower although significant only for noradrenaline in diabetic (the gray square) compared to nondiabetic (the white square) rats. Figures are reproduced from Abdulla et al [16] and Armenia et al [144] respectively. Data, mean ± SEM represent the overall mean of responses to a range of doses from each agonist.…”

Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury—beyond the direct renin inhibition

“…The experimental group received renal artery ligation surgery 19 and the control mice received sham surgery. Mice in the experimental group were assigned randomly into two groups: aliskiren treatment group (n¼8) and non-treatment group (n¼8).…”