Functional Subtypes of Renal α₁-Adrenoceptor in Spontaneously Hypertensive Rats with Streptozotocin-Induced Experimental Diabetic Nephropathy

Abstract

Aim: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal α₁-adrenoceptor subtype composition. Methods: In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na⁺ (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (α-adrenoceptor agonist), phenylephrine (α₁-adrenoceptor agonist) and methoxamine (α_1A-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca²⁺ channel blocker), 5-methylurapidil (α_1A-adrenoceptor antagonist), chloroethylclonidine (α_1B-adrenoceptor antagonist) and BMY 7378 (α_1D-adrenoceptor antagonist). Results: In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses. Conclusion: The data demonstrated that there was a functional coexistence of α_1A- and α_1D-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic α-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR.

Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats

“…In the experimentally induced diabetic rats, a significant reduction in the body weight was observed, whereas, STZ lead to same degree of hyperglycemia in all experimental groups. This finding is consistent with the earlier studies of our laboratory that the weight loss is one of the common happening in STZ induced diabetes in rats (32), (33). In a state of experimental diabetes such as type 1, most of β -cells are destroyed leading to hypoinsulinemia and hyperglycaemia due to the decreased utilization of the glucose by the tissues and will lead to reduction in body weight (34).…”

“…Interestingly, with the induction of diabetes, SHR diabetic groups exhibited decreased renal cortical blood perfusion (RCBP) and it is in agreement with our previous lab findings (33), which is due to the increased renovascular response to adrenergic and neural stimuli and activation of intra-renal RAAS (41). The hyperglycemia induced by STZ lead to activation of local ANG II (42), which cause increased renovascular resistance, thus leads to reduced RCBP in diabetic rats.…”

“…Diabetic rats expressed low urinary sodium (UNaV), demonstrating renal impairment of sodium handling which is in consent with the previous report of Khan (33). We understand that kidneys regulates the long-term B.P through altered renal sodium handling to conserve the sodium-retaining characteristics (44), whereas, diabetes leads to renal pathologies via renal imbalance of vital electrolytes in the form of sodium retention (45).…”

Exogenous Hydrogen Sulfide (H2S) Reduces Blood Pressure and Prevents the Progression of Diabetic Nephropathy in Spontaneously Hypertensive Rats

“…10 Plasma creatinine 26 and creatinine clearance, a measure of glomerular filtration rate (GFR), 8 are commonly used to evaluate the renal hemodynamic function. Khan et al 27 reported that the SHR-STZ model of genetic hypertension and diabetes is one which develops the typical changes in renal injury early in the course of the disease. Interestingly, we have also demonstrated renal injury in terms of increased plasma creatinine and creatinine clearance in the diabetic SHR group.…”

Exogenous adiponectin with full Peroxisome proliferator-activated receptor agonists (pioglitazone) abrogates streptozotocin induced oxidative stress and vascular abnormalities in Spontaneously hypertensive rats.

“…Physiological and metabolic indices were kept into consideration to assess the experimental diabetes in SHRs, including body weight, which was signi cantly reduced as one of the pronounced effect of STZ on β -cells (38). Polyuria and polydipsia were also observed as signi cant metabolic perturbations of diabetic SHRs and found to be in accordance with the observations of Khan (39).…”