I030 Young spontaneously hypertensive rats (SHR) with chronic inhibition of nitric oxide exhibit similar aortic stiffness to old SHR

Abstract

The old spontaneously hypertensive rat (SHR) is known to be a good experimental model that is highly analogous to essential hypertension in man but is costly and time consuming. Chronic inhibition of nitric oxide (NO) production in young adult SHR is an experimental model of malignant hypertension and chronic renal disease, very similar to old SHR1. Considering that acute or chronic decreases in NO production in normotensive rats increase arterial stiffness, we aimed to compare the aortic stiffness between SHR/L-NAME and old SHR. Male SHR (18 weeks old) received N-Nitro-L-Arginine Methyl Ester (L-NAME) 6 mg/kg/d in drinking water (SHR/L-NAME) for 2 weeks and were compared to SHR and Wistar Kyoto rats (WKY). Moreover, two groups are composed of 55 weeks aged SHR (Old SHR) and WKY (Old WKY). Under anesthesia, two catheters were introduced in the left common carotid artery and the left femoral artery to measure central and peripheral blood pressure and assess aortic stiffness with pulse wave velocity (PWV= distance between the tips of the two catheters / transit time), β-index (2.11×(PWV2/Diastolic blood pressure)), amplification and pulse pressure (PP). At 20 weeks, although SHR have higher central systolic blood pressure (SBP) than WKY (201±7 mmHg vs. 154±4 mmHg), no significant difference in PWV, PP, amplification and β-index was observed between these two groups. With age, old WKY have higher SBP (181±8 mmHg) and higher PWV (6.7±0.5 m/s) and β-index (0.70±0.08) than young WKY. Old SHR exhibit higher SBP (252±13 mmHg), PWV (9.3±0.7 m/s), PP (71±7 mmHg), β-index (1.08±0.16) than old WKY and young SHR (PWV=6.3±0.2 m/s, PP=39±3 mmHg and β-index=0.50±0.03). Young SHR, after 2 weeks of L-NAME administration, have higher SBP (238±10 mmHg) and aortic stiffness (PWV=8.6±0.6 m/s, PP=54±6 mmHg and β-index=0.89±0.14) than young SHR and possess the aortic stiffness observed in old SHR. In conclusion, our results indicate a close analogy in arterial stiffness between SHR/L-NAME and old SHR. Thus, this experimental model shows similarities to hypertensive humans and appears relevant to test new anti-hypertensive treatments.