Direct Vasodepressor Effects of Pioglitazone in Spontaneously Hypertensive Rats

Abstract

Effects of pioglitazone on plasma insulin levels, systolic blood pressure and arterial reactivity were studied in spontaneously hypertensive (SH) rats. Chronic treatment of SH rats with pioglitazone decreased plasma insulin levels and blood pressure. Direct effects of pioglitazone on vascular reactivity were also studied in aortae and superior mesenteric arteries from SH rats. Pioglitazone markedly inhibited arginine vasopressin (AVP) and norepinephrine (NE) responses without affecting responses to potassium chloride (KCl). These data suggest that (a) antihypertensive effects of pioglitazone in SH rats may be mediated via a direct vasodepressor effect, and (b) vasodilation may be coupled to insulin sensitivity in SH rats.

Regulation of Cytochrome P-450 4A Activity by Peroxisome Proliferator-Activated Receptors in the Rat Kidney

“…(27)(28)(29)(30)(31). It is generally thought that thiazolidinediones exert their antihypertensive effect by improving insulin-stimulated sodium retention in the renal tubules (49) and acting directly on the vasculature (27,29,30,50). Although, based on the present results, there is a slight possibility that 20-HETE mediates the antihypertensive effect of thiazolidinediones, further studies will be needed to examine the expression of PPARγ protein and the inducibility of P-450 4A by thiazolidinediones in the kidney of obese and diabetic rats.…”

“…Clofibrate (the PPARα agonist, 400 mg/kg per day) and pioglitazone (the PPARγ agonist, 20 mg/kg per day) were administrated orally for 2 weeks. These doses of clofibrate and pioglitazone have been reported to significantly decrease systemic blood pressure in rats (23,(29)(30)(31). All protocols involving rats were reviewed and received prior approval by the Animal Welfare Committee at the Tohoku University School of Medicine.…”

“…In contrast to fibrates, thiazolidinediones, the antidiabetic drugs, are selective agonists for PPARγ (26). These drugs also decrease blood pressure and proteinuria and prevent glomerular injury in Zucker obese rats (27,28), spontaneously hypertensive rats (29), Dahl saltsensitive rats (30) and Wistar fatty rats (31). However, it has not been determined whether thiazolidinediones can induce P-450 4A mRNAs and proteins in vivo, or whether 20-HETE can mediate the antihypertensive and renal-protective effects of thiazolidinediones.…”

Pioglitazone enhances the blood pressure-lowering effect of losartan via synergistic attenuation of angiotensin II-induced vasoconstriction

“…Several experimental studies have shown that pioglitazone has an antihypertensive effect in insulin-resistant and/or hypertensive animal models. [1][2][3][4][5][6][7][8][9][10] Clinical studies have reported that pioglitazone is either neutral [11][12][13] or associated with a mild decrease [14][15][16][17] in blood pressure (BP). The BP-lowering effect of pioglitazone has been described in patients with type 2 diabetes, 14 type 2 diabetics with difficult-to-control hypertension, 15 nondipping diabetic patients, 16 and patients with congenital adrenal hyperplasia.…”

Inhibition of Vascular Angiotensin-Converting Enzyme by Telmisartan via the Peroxisome Proliferator-Activated Receptor .GAMMA. Agonistic Property in Rats

“…We found here that the partial PPARγ agonist telmisartan significantly reduced ACE activity in sodium-loaded SHR-SP, whereas the non-PPARγ agonist valsartan did not. Other reports have shown that PPARγ ligands significantly reduce blood pressure in hypertensive rats without diabetes or obesity (12)(13)(14). These findings suggest that telmisartan exerts its hypotensive effect through vascular ACE inhibition via the PPARγ agonistic effect.…”