Pulse pressure, aortic reactivity, and endothelium dysfunction in old hypertensive rats.
The reactivity of old hypertensive rat aortas has not been investigated in relation to each phenotype of the blood pressure curve, mean arterial pressure (MAP), and pulse pressure (PP). Aortic reactivities from 3- to 78-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were studied with the use of organ chambers and invasive blood pressure, carotid diameter, and histomorphometry. MAP and PP were elevated in SHR, but at 78 weeks, a selective increase of PP without further MAP increase was observed for the same carotid diameter as WKY. Aortic relaxation in response to carbamylcholine decreased similarly with age in both strains. With (+) or without (-) endothelium (E), maximal developed tension (MDT) under KCl increased linearly with age in SHR, proportionally to wall thickness and MAP increase. Under norepinephrine (NE), MDT of E(-) aortas from SHR and controls increased with age and reached plateaus at 12 weeks, whereas MDT of E(+) aortas from SHR increased linearly with age. Because the NE-induced MDT was higher for E(-) than E(+), the difference estimated endothelial function. This difference reached plateaus from 12 to 78 weeks in WKY but was abolished beyond 12 weeks in SHR, a finding also observed under NO-synthase inhibition. In old hypertensive rats, (1) increased KCl reactivity is endothelium independent but influenced by the MAP-dependent aortic hypertrophy with resulting increased vascular smooth muscle reactivity, whereas (2) increased NE reactivity is endothelium dependent in association with increased PP, altered endothelial function, and extracellular matrix, with resulting enhanced intrinsic arterial stiffness.
Chamiot-Clerc
P
P
Medical Research Department, CNRS ESA 8078, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France.
Renaud
J F
JF
Safar
M E
ME
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D001013:Aorta, Thoracic / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002339:Carotid Arteries / Q000033:anatomy & histology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011673:Pulsatile Flow / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D002217:Carbachol; D009638:Norepinephrine