title: Age and hypertension strongly induce aortic stiffening in rats at basal and matched blood pressure levels.
abstract: Age and hypertension are major causes of large artery remodeling and stiffening, a cardiovascular risk factor for heart and kidney damage. The aged spontaneously hypertensive rat (SHR) model is recognized for human cardiovascular pathology, but discrepancies appeared in studies of arterial stiffness. We performed experiments using a robust analysis via echo tracking in 20-week adult (n = 8) and 80-week-old SHR (n = 7), with age-matched normotensive Wistar Kyoto rats (WKY, n = 6;6) at basal and matched levels of blood pressure (BP). After anesthesia with pentobarbital, abdominal aortic diameter and pressure were recorded and BP was decreased by clonidine i.v. At basal BP, aortic pulse distension, compliance, and distensibility (AD) were reduced and stiffness index increased with age and hypertension and further altered with age + hypertension. When BP was adjusted in SHR to that of normotensive rats (130 mmHg), there was no difference between 20-week-old SHR and WKY Importantly, the age effect was maintained in both WKY and SHR and accentuated by hypertension in old rats. At 130 mmHg, with similar pulse pressure in the four groups, AD (kPa(-3)) = 24.2 ± 1 in 20 weeks WKY, 19.7 ± 1.4 in 20 weeks SHR, 12.4 ± 1.3 in 80 weeks WKY and 6.6 ± 0.6 in 80 weeks SHR; distension = 7.6 ± 0.4%, 6.7 ± 0.6%, 3.7 ± 0.3%, and 1.8 ± 0.2% in the same groups. In conclusion, reduced distensibility, that is, stiffening due to age is clearly shown here in both WKY and SHR as well as a synergistic effect of age and hypertension. This technique will allow new studies on the mechanisms responsible and drug intervention.
authors.affiliation: Cardiovascular Discovery Research Unit, Servier Research Institute, Suresnes, France.
authors.forename: George
authors.initials: G
authors.lastname: Lindesay
authors.affiliation: Cardiovascular Discovery Research Unit, Servier Research Institute, Suresnes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ragonnet
authors.affiliation: Cardiovascular Discovery Research Unit, Servier Research Institute, Suresnes, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Chimenti
authors.affiliation: Cardiovascular Discovery Research Unit, Servier Research Institute, Suresnes, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Villeneuve
authors.affiliation: Cardiovascular Discovery Research Unit, Servier Research Institute, Suresnes, France christine.courchay@servier.com.
authors.forename: Christine
authors.initials: C
authors.lastname: Vayssettes-Courchay
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D059289:Vascular Stiffness / Q000502:physiology*
keywords: Age; aortic distensibility; aortic stiffness; echo tracking; hypertension; spontaneously hypertensive rat