Effect of Angiotensin II Type 1 Receptor Blockade on Conduit Artery Tone in Subtotally Nephrectomized Rats

Abstract

Background: Angiotensin II type 1 (AT₁) receptor antagonists provide end-organ protection and enhance resistance artery relaxation in uremia. The effect of AT₁ blockade on conduit artery function in renal failure is unknown. Methods: The influence of 8-week losartan therapy (20 mg/kg/day) on tone of isolated main branch mesenteric arterial rings was studied in 5/6 nephrectomized (NX) rats. Blood and urine chemistry were examined, and AT₁ receptors quantified using autoradiography. Results: NX rats showed decreased creatinine clearance without change in blood pressure. Losartan did not influence these variables, although [¹²⁵I]-Sar1,Ile8-angiotensin II binding to renal AT₁ receptors was significantly prevented. Vasoconstriction to endothelin-1 was reduced by losartan in NX and Sham rats. Vasorelaxation to acetylcholine was attenuated in untreated but not in losartan-treated NX rats, and experiments with Ca²⁺-activated K⁺ channel blockers suggested that impaired endothelium-mediated response after NX was due to deficient relaxation via K⁺ channels. Endothelium-independent relaxation to levcromakalim, adenosine triphosphate-sensitive K⁺ channel agonist, was impaired in untreated but not in losartan-treated NX rats. Conclusion: Losartan reduced conduit artery vasoconstriction to endothelin-1 and augmented vasorelaxation via K⁺ channels in NX rats, although blood pressure and renal function were unchanged. Therefore, AT₁ blockade confers functional benefits to large arteries in renal failure.

Paricalcitol Treatment and Arterial Tone in Experimental Renal Insufficiency

“…In the 1–2 distal rings the endothelium was left intact, and from the proximal pieces it was removed mechanically [22]. The rings were suspended between hooks in a standard organ bath chamber, and resting preload was adjusted to 4.905 mN/mm [22].…”

Vasopeptidase Inhibition Corrects the Structure and Function of the Small Arteries in Experimental Renal Insufficiency

“…The NX rats showed several characteristic findings of moderate renal insufficiency (table 1; figs. 2, 3, 4) [33,41], while omapatrilat treatment effectively reduced heart weight, BP and BNP levels in experimental CRI. Omapatrilat treatment also improved vascular morphology and function in the small arteries and endothelium-independent vasodilatation was also enhanced compared to both the untreated NX rats and the Sham controls.…”

Effects of oxonic acid-induced hyperuricemia on mesenteric artery tone and cardiac load in experimental renal insufficiency

“…The large arterial rings were equilibrated in a resting preload of 4.905 mN/mm [ 16 ], while the small arterial preparations were normalized so that the internal diameter of the vessel was set at 90% of that obtained when exposed to intraluminal pressure of 100 mmHg in the relaxed state [ 15 , 17 ]. In the large arteries, the force of contraction was measured with isometric force-displacement transducer and registered on a polygraph (FT 03 transducer, 7E Polygraph; Grass Instrument Co., Quincy, MA, USA) and in the small arteries the computerized Mulvany multimyograph (Model 610A, J.P. Trading, Aarhus, Denmark) was employed [ 16 ]. All arterial preparations were kept in physiological salt solution (PSS, pH 7.4) containing (mM): NaCl 119.0, NaHCO 3 25.0, glucose 11.1, CaCl 2 1.6, KCl 4.7, KH 2 PO 4 1.2, MgSO 4 1.2, and aerated with 95% O 2 and 5% CO 2 at 37°C.…”

“…In experimental CRI, reduced vasodilatation via Ca 2+ -activated K + -channels (BK Ca ), observed in isolated mesenteric arterial branches, may precede the elevation of blood pressure (BP) [ 15 , 16 ]. However, until now the vascular effects of UA have only been studied in arteries in which the endothelium-mediated dilatation is mainly mediated via NO [ 12 , 14 ].…”