The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats.
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 alpha(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 x kg(-1) 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 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), 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 P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(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, alpha(1B)-, and/or alpha(2)-subtypes.
Armenia
A
A
School of Pharmaceutical Sciences, University of Science Malaysia, 11800 Penang, Malaysia.
Munavvar
A S
AS
Abdullah
N A
NA
Helmi
A
A
Johns
E J
EJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000379:methods; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply* / Q000294:innervation / Q000503:physiopathology; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects; D008296:Malaysia; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009568:Nitrendipine / Q000008:administration & dosage / Q000493:pharmacokinetics; D009638:Norepinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics; D010656:Phenylephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D011918:Rats, Inbred SHR; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D010656:Phenylephrine; C051731:chlorethylclonidine; D013311:Streptozocin; D009568:Nitrendipine; D008729:Methoxamine; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine