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 press ure (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 observe d for the same carotid diameter as WKY. Aortic relaxation in response to ca rbamylcholine decreased similarly with age in both strains. With (+) or wit hout (-) endothelium (E), maximal developed tension (MDT) under KCl increas ed linearly with age in SHR, proportionally to wall thickness and MAP incre ase. Under norepinephrine (NE), MDT of E- aortas from SHR and controls incr eased with age and reached plateaus at 12 weeks, whereas MDT of E+ aortas f rom SHR increased linearly with age. Because the NE-induced MDT was higher for E- than E+, the difference estimated endothelial function. This differe nce 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 incr eased vascular smooth muscle reactivity, whereas (2) increased NE reactivit y is endothelium dependent in association with increased PP, altered endoth elial function, and extracellular matrix, with resulting enhanced intrinsic arterial stiffness.