title: Interaction between irbesartan, peroxisome proliferator-activated receptor (PPAR-γ), and adiponectin in the regulation of blood pressure and renal function in spontaneously hypertensive rats.
abstract: Adiponectin exerts vasodilatory effects. Irbesartan, an angiotensin receptor blocker, possesses partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity and increases circulating adiponectin. This study explored the effect of irbesartan alone and in combination with adiponectin on blood pressure, renal hemodynamic excretory function, and vasoactive responses to angiotensin II and adrenergic agonists in spontaneously hypertensive rat (SHR). Irbesartan was given orally (30 mg/kg/day) for 28 days and adiponectin intraperitoneally (2.5 μg/kg/day) for last 7 days. Groups of SHR received either irbesartan or adiponectin or in combination. A group of Wistar Kyoto rats (WKY) served as controls. Metabolic data and plasma samples were taken on days 0, 21, and 28. In acute studies, the renal vasoconstrictor actions of angiotensin II (ANGII), noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) were determined. SHR control rats had a higher mean blood pressure than the WKY (132 ± 7 vs. 98 ± 2 mmHg), lower plasma and urinary adiponectin, creatinine clearance, urine flow rate and sodium excretion, and oxidative stress markers compared to WKY (all P < 0.05) which were progressively normalized by the individual drug treatments and to a greater extent by combined treatment. Responses to intrarenal administration of NA, PE, ME, and ANGII were larger in SHR (P < 0.05) than WKY by 20-25 %. Irbesartan enhanced (P < 0.05) responses to NA and PE, while adiponectin blunted responses to all vasoconstrictors (all P < 0.05). Combined treatment in SHR further decreased the renal vascular responses to ANGII. These findings suggest that an interactive relationship may exist between PPAR-γ, alpha adrenoceptors, and ANGII in the renal vasculature of the SHR.
authors.affiliation: Cardiovascular and Renal Physiology Lab, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia. samalik77@hotmail.com.
authors.forename: S
authors.identifier: http://orcid.org/0000-0001-8387-7550
authors.initials: S
authors.lastname: Afzal
authors.affiliation: Cardiovascular and Renal Physiology Lab, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia.
authors.forename: M A
authors.initials: MA
authors.lastname: Sattar
authors.affiliation: Department of Physiology, University College Cork, Cork, Ireland.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Johns
authors.affiliation: Department of Physiology, University College Cork, Cork, Ireland.
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Abdulla
authors.affiliation: Cardiovascular and Renal Physiology Lab, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia.
authors.forename: Safia
authors.initials: S
authors.lastname: Akhtar
authors.affiliation: Cardiovascular and Renal Physiology Lab, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia.
authors.forename: Fayyaz
authors.initials: F
authors.lastname: Hashmi
authors.affiliation: Department of Pharmacology, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.
authors.forename: Nor Azizan
authors.initials: NA
authors.lastname: Abdullah
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000284:Administration, Oral; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005786:Gene Expression Regulation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013777:Tetrazoles / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D047495:PPAR gamma; D011942:Receptors, Adrenergic, alpha; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D010656:Phenylephrine; D008729:Methoxamine; D000077405:Irbesartan; D009638:Norepinephrine
keywords: Adiponectin; Angiotensin II; Peroxisome proliferator-activated receptor; Renal hemodynamics; Spontaneously hypertensive rat (SHR)