The effects of quinapril and atorvastatin on artery structure and function in adult spontaneously hypertensive rats.
We studied the combined treatment effects of quinapril and atorvastatin on blood pressure and structure and function of resistance arteries from adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY rats). Apoptotic cells were identified by in situ end labeling using the terminal deoxynucleotide transferase-mediated dUTP nick end labeling method. Vascular structure was measured using a morphometric protocol and confocal microscopy and a pressurized artery system was used to study vascular functions. We found that a combined treatment with quinapril and atorvastatin lowered systolic blood pressure in both adult SHR and WKY rats and decreased medial thickness and volume and the number of smooth muscle cell layers in mesenteric arteries, as well as media-to-lumen ratio in the interlobular arteries from SHR but not in those from WKY rats. The number of apoptotic smooth muscle cells was higher in the mesenteric arteries from control WKY rats than control SHR and treatment increased the number of apoptotic smooth muscle cells in the arteries from both SHR and WKY rats. Treatment with quinapril and atorvastatin reduced ventricular weight in SHR and normalized the augmented contractile responses to norepinephrine but did not alter the contraction to electric field stimulation. Relaxation responses to acetylcholine and sodium nitroprusside were not affected by the treatment. We conclude that a combined treatment with quinapril and atorvastatin lowered blood pressure and improved cardiac and vessel hypertrophy and vessel function. An increase in apoptotic smooth muscle cells may be one of the mechanisms underlying the structural improvement.
Yang
Lufang
L
Smooth Muscle Research Programme and Department of Anaesthesia, (HSC-2U3), McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Gao
Yu-Jing
YJ
Lee
Robert M K W
RM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001158:Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D018613:Microscopy, Confocal; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D044005:Tetrahydroisoquinolines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000069059:Atorvastatin; D000109:Acetylcholine; D000077583:Quinapril; D009638:Norepinephrine