Abstract
The effects of chronic treatment with quinapril on blood pressure, vascular reactivity and structure of resistance arteries were examined in adult, male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR and WKY at 15 weeks of age were treated with quinapril (10 mg/kg per day) for 10 weeks. Structural changes in the mesenteric arteries were measured by optical sectioning with confocal microscopy and in renal arteries by light microscopic measurements. Apoptotic cells in the mesenteric vessel wall were identified using the terminal deoxynucleotide transferase-mediated dUTP-nick end-labelling (TUNEL) method. The response of mesenteric arteries to noradrenaline, electrical stimulation, acetylcholine and sodium nitroprusside was studied using a pressure myograph system. Treatment with quinapril significantly lowered systolic blood pressure and ventricular weight in both SHR and WKY. It reduced wall thickness and medial volume in mesenteric arteries from SHR and WKY and media-to-lumen ratio in interlobular arteries of SHR. It also decreased the number of smooth muscle layers in SHR and increased the number of apoptotic smooth muscle cells in both SHR and WKY. In addition, treatment normalized the augmented contractile responses and improved the impaired relaxation response of SHR mesenteric arteries to the level of WKY. We conclude that treatment with quinapril lowered blood pressure and improved cardiac and vessel structure and vessel function. An increase in apoptotic process of medial smooth muscle cells is one of the mechanisms underlying the vascular structural improvement.
Similar content being viewed by others
References
Bennett MA, Thurston H (1996) Effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in two-kidney, one-clip Goldblatt hypertensive and sham-operated rats. Clin Sci (Lond) 90:21–29
Campbell DJ, Kladis A, Duncan A-M (1994) Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides. Hypertension 23:439–449
Cho A, Mitchell L, Koopmans D, Langille BL (1997) Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits. Circ Res 81:328–337
DeBlois D, Tea BS, Dam TV, Tremblay J, Hamet P (1997) Smooth muscle apoptosis during vascular regression in spontaneously hypertensive rats. Hypertension 29:340–349
Dickhout JG, Lee RMKW (1997) Structural and functional analysis of small arteries from young spontaneously hypertensive rats. Hypertension 29:781–789
Dickhout JG, Lee RM (1999) Apoptosis in the muscular arteries from young spontaneously hypertensive rats. J Hypertens 17:1413–1419
Dickhout JG, Lee RM (2000) Increased medial smooth muscle cell length is responsible for vascular hypertrophy in young hypertensive rats. Am J Physiol 279:H2085–H2094
Díez J, Panizo A, Hernández M, Galindo MF, Cenarruzabeitia E, Mindán FJP (1997) Quinapril inhibits c-myc expression and normalizes smooth muscle cell proliferation in spontaneously hypertensive rats. Am J Hypertens 10:1147–1152
Dukacz SA, Feng MG, Yang LF, Lee RM, Kline RL (2001) Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment. Am J Physiol 280:R1076–R1084
Lee RMKW (1985) Vascular changes at the prehypertensive phase in the mesenteric arteries from spontaneously hypertensive rats. Blood Vessels 22:105–126
Lee RMKW, Garfield RE, Forrest JB, Daniel EE (1983) Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats. Blood Vessels 20:57–71
Lee RMKW, Berecek KH, Tsoporis J, McKenzie R, Triggle CR (1991) Prevention of hypertension and vascular changes by captopril treatment. Hypertension 17:141–150
Major TC, Overhiser RW, Taylor DG Jr, Panek RL (1993) Effects of quinapril, a new angiotensin-converting enzyme inhibitor, on vasoconstrictor activity in the isolated, perfused mesenteric vasculature of hypertensive rats. J Pharmacol Exp Ther 265:187–193
Ohwada T, Ishibashi T, Yaoita H, Shindo J, Noji H, Ohkawara H, Sugimoto K, Sakamoto T, Maehara K, Maruyama Y (2002) Different contribution of apoptosis to the antiproliferative effects of l-arginine, enalapril and losartan on neointimal growth inhibition after balloon arterial injury. Circ J 66:965–971
Smeda JS (1992) Cerebral vascular changes associated with hemorrhagic stroke in hypertension. Can J Physiol Pharmacol 70:552–564
Zakeri ZF, Ahuja HS (1994) Apoptotic cell death in the limb and its relationship to pattern formation. Biochem Cell Biol 72:603–613
Acknowledgments
We thank Parke-Davis Pharmaceutical Research, Division of Warner Lambert Canada Ltd. and Pfizer Canada for the generous gift of quinapril and their financial support, and our summer student Ms Nermin Attia for part of the functional study experiment of mesenteric arteries.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, L., Gao, YJ. & Lee, R.M.K.W. Quinapril effects on resistance artery structure and function in hypertension. Naunyn-Schmiedeberg's Arch Pharmacol 370, 444–451 (2004). https://doi.org/10.1007/s00210-004-0990-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-004-0990-x