Contractility and endothelium-dependent relaxation of resistance vessels in polycystic kidney disease rats.
Hypertension and vascular disease are common complications in autosomal-dominant polycystic kidney disease (ADPKD). The role of changes in morphology and reactivity of resistance vessels in this disease have not previously been studied. Mesenteric resistance arteries were dissected from 8- to 14-week-old heterozygous Han:SPRD polycystic kidney disease (PKD) rats, homozygous normal Han:SPRD littermates (HSPRD) and Sprague-Dawley rats (SD). The morphology, noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) relaxation before and after incubation with L(G)-nitro-L-arginine methyl ester (L-NAME), and endothelium-independent 3-morphollino-sydnonimine (SIN-1) relaxation were studied with the Mulvany-Halpern myograph. Blood pressure and morphology of vessels were the same in all groups of rats, apart from a slightly higher media/lumen ratio in heterozygous PKD rats (p < 0.05). Active wall tension and contractile sensitivity to NA were higher in both heterozygous PKD rats and HSPRD than SD rats (p < 0. 05). The maximum endothelium-dependent relaxation rate was markedly decreased in heterozygous PKD (19 +/- 9%) and HSPRD (34 +/- 12%) compared to SD rats (75 +/- 11%) (p < 0.05). After incubation with L-NAME, ACh-induced relaxation was significantly attenuated in SD rats, less attenuated in HSPRD, and not significantly changed in heterozygous PKD rats. SIN-1-induced endothelium-independent relaxation was similar in all three groups. In conclusion, hyperreactivity to NA and impaired endothelium-dependent relaxation were present in resistance vessels from Han:SPRD rats, especially in animals with PKD. These abnormalities in resistance vessels from PKD rats may be important for the development of hypertension and vascular disease.
Wang
D
D
Department of Nephrology, Herlev Hospital, University Hospital of Copenhagen, Denmark. wangdan9090@hotmail.com
Iversen
J
J
Strandgaard
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D007668:Kidney / Q000473:pathology / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D007690:Polycystic Kidney Diseases / Q000503:physiopathology*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; C002385:linsidomine; D008981:Molsidomine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester