Abstract 543: Increased Aortic Pulse Wave Velocity in Type 2 Diabetic db/db Mice is Dependent on Blood Pressure

Abstract

Pulse wave velocity (PWV) is the gold standard for in vivo aortic stiffness measurements but can be dependent upon blood pressure and/or heart rate. Previous studies from our and other labs have shown increased aortic PWV in type 2 diabetic db/db mice. Moreover, preliminary ex vivo pressure myography data from our lab has also shown a lack of increase in passive aortic stiffness, suggesting that increased PWV in vivo , and therefore, increased stiffness in db/db mice may be dependent upon other mechanisms. In this study, we tested the hypothesis that increased aortic pulse wave velocity measured in db/db mice in vivo is blood pressure dependent under anesthesia. 16-wk old normal Db/db (n=9) and type 2 diabetic db/db (n=5) mice were anesthetized with 2% isoflurane and instrumented with two 1.2F pressure-tip catheters: one inserted in the left carotid artery and advanced to the thoracic aorta, the other inserted into the left femoral artery and advanced into the abdominal aorta. Blood pressure was continuously recorded and PWV was calculated using the foot-to-foot method. A microcannula was inserted into the right jugular vein for the administration of drugs. After a stabilization period of 25-30 mins, baseline BPs and PWVs were measured, after which mice were infused with increasing doses of phenylephrine (Phe, 100-500 nmol/kg/min) and sodium nitroprusside (SNP, 100-500 nmol/kg/min) to increase and decrease blood pressure, respectively. At baseline (prior to the infusion of any drugs), mean arterial pressure and aortic PWV were significantly elevated in db/db mice under anesthesia (MAP; Db/db: 77±5 vs. db/db: 100±4 mmHg, p <0.05; PWV; Db/db: 0.31±0.01 vs. db/db: 0.35±0.01 cm/ms, p <0.05). The increase in aortic PWV in db/db mice at baseline was completely abrogated when measured at equivalent MAPs ranging from 40-120 mmHg during the Phe and SNP infusions ( p >0.05). In both Db/db and db/db mice, aortic PWV was significantly correlated with MAP (Db/db: r=0.94, p <0.001; db/db: r=0.97, p <0.0001). These data show that increased aortic PWV, and therefore increased aortic stiffness in db/db mice in vivo is dependent upon blood pressure.