title: Altered renal microvascular response in Zucker obese rats.
abstract: Although available evidence demonstrates that obesity manifests insulin resistance and causes glomerular sclerosis, it has not been determined whether insulin resistance alters the renal microvascular reactivity. This study examined whether insulin- and acetylcholine (ACH)-induced vasodilation was impaired in Zucker obese rats, and attempted to clarify the change in myogenic afferent arteriolar constriction, a determinant of glomerular pressure. Isolated perfused hydronephrotic rat kidneys were used to visualize the renal microcirculation. In Zucker lean rats, insulin (10 to 300 microU/mL) inhibited norepinephrine (NE)-induced afferent and efferent arteriolar constriction in a dose-dependent manner, with 112 % +/- 8% and 98% +/- 8% reversal at 300 microU/mL Similarly, ACH elicited dose-dependent dilation of these vessels. In Zucker obese rats, by contrast, afferent and efferent arterioles failed to dilate in response to insulin, and manifested diminished vasodilator responses to acetylcholine In the presence of nitro-L-arginine methylester (LNAME; 100 micromol/L), ACH (10 micromol/L) induced transient afferent arteriolar dilation (121% +/- 9% reversal) in Zucker lean rats, whereas this response was blunted in obese rats (72% +/- 8% reversal) Furthermore, myogenic afferent arteriolar constriction by elevating renal arterial pressure to 180 mm Hg was diminished in Zucker obese rats (-14% +/- 3% decrement in diameter), compared with that in lean rats (-23% +/- 2% decrement) Finally, the impairment in these vasodilator and vasoconstrictor responses was partially prevented by troglitazone, an insulin-sensitizing agent. Collectively, in insulin resistance, renal microvessels are refractory to the vasodilator action of insulin. Furthermore, "renal insulin resistance" is associated with the impaired vasodilator responses to ACH-induced nitric oxide (NO) and the diminished vasoconstrictor responses to pressure. The blunted myogenic afferent arteriolar constriction would allow glomerular hypertension, and in concert with the impaired endothelium-dependent vasodilation, could be responsible for the development of glomerular injury in obesity.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanda
authors.forename: Koichiro
authors.initials: K
authors.lastname: Homma
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Ken
authors.initials: K
authors.lastname: Okubo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takamatsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Tatematsu
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kumagai
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D006869:Hydronephrosis / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker / Q000502:physiology*; D012016:Reference Values; D012077:Renal Artery / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002839:Chromans; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077288:Troglitazone; D000109:Acetylcholine; D009638:Norepinephrine