Augmentation of Pulse Wave Velocity Precedes Vascular Structural Changes of the Aorta in Rats Treated with N.OMEGA.-Nitro-L-Arginine Methyl Ester

Abstract

We examined the relationship between structural changes of the aorta and pulse wave velocity (PWV), and the effects of antihypertensive treatments on PWV in N S S S S -nitro-L -arginine methyl ester (L-NAME)-treated rats.Twelve-week-old Wistar-Kyoto (WKY) rats were divided into the following groups, all of which received drug treatment in their drinking water: an untreated control group ( n = 36), an L-NAME-treated group (0.7 mg/ml) ( n = 32), an L-NAME and angiotensin converting enzyme (ACE) inhibitor (ACEI)-treated group (imidapril: 0.4 mg/ml) ( n = 8), and an L-NAME and hydralazine-treated group (0.2 mg/ml) ( n = 10). PWV was measured at the same blood pressure (BP) level as in the control group and the wall-to-lumen ratio of the thoracic aorta was evaluated in all groups. In the L-NAME group, PWV increased compared with the value in the control group, at the same time that BP was increasing. After the third day of treatment, PWV was higher in the L-NAME group than in the control group after adjusting BP to the control level, while the wall-to-lumen ratios were equal between the two groups. After the first week of treatment, not only the adjusted PWV, but also the wall-to-lumen ratios were greater in the L-NAME group than in the control group. With administration of antihypertensive agents, both PWV and the thickening of the aortic wall were reduced, but there was no significant difference between the ACEI and hydralazine-treated groups. In conclusion, in a rat model of nitric

Direct Angiotensin II Type 2 Receptor Stimulation in N ω -Nitro- l -Arginine-Methyl Ester–Induced Hypertension

“…4 PWV is considered the best and direct marker of arterial stiffness. 3 Both experimental 27 and clinical hypertension 34,35 are associated with increased PWV. The PWV is considered to be an independent cardiovascular risk factor not only in hypertensives 36,37 but also in end-stage renal disease patients, 38 in the elderly, 39 and even in the general population.…”

“…25 The wall thickening was accompanied by reduced ID, slightly increased aortic cross-sectional area, and most importantly increased WT/ID ratio in accordance with previous studies on this model of hypertension. 27,48 In our study we have investigated the effects of the AT 2 R agonist on PWV in L-NAME rats. Direct AT 2 R stimulation was already reported to reduce the extent of myocardial infarction and to improve cardiac function along with antiinflammatory effects in rats.…”

“…16 -21 In vivo inhibition of NO synthase by treating animals with N -nitro-L-arginine-methyl ester (L-NAME) provides a wellestablished model of hypertension, [22][23][24] vascular wall remodeling, 25,26 and PWV increase. 27,28 Using this model, we aimed to investigate the effects of long-term direct AT 2 R stimulation by the novel nonpeptide AT 2 R agonist, compound 21, on aortic remodeling and PWV in L-NAME-treated rats. Furthermore, we aimed to compare the effects of AT 2 R stimulation to the effects of the AT 1 R antagonist, olmesartan, and to evaluate the effects of the combination treatment with compound 21 and olmesartan.…”

Applanation Tonometry in Mice

“…Elevated aPWV caused by endothelial dysfunction was reported earlier in mice, 12,22 and several studies in rats indicate that the reduced bioavailability of nitric oxide is a key factor in the development of large artery stiffness. 7,8,12,24,25 It was also reported earlier that Nembutal-anesthetized WT mice have a lower PWV compared with WT mice sedated with other anesthetic agents. 10 In the present study, we were able to confirm these observations using applanation tonometry.…”

“…However, PWV assessment in mice, which are regularly used in preclinical research of cardiovascular disease, is less straightforward because of the small size and high heart rate of 400 to 600 bpm. Here, invasive intravascular tonometry can be used to measure aortic PWV (aPWV) or cfPWV, [6][7][8][9] but it cannot be applied in longitudinal studies. To determine aPWV noninvasively in mice, most frequently, ultrasonic echo Doppler velocimetry is used.…”