Neonatal oxygen exposure leads to increased aortic wall stiffness in adult rats: a Doppler ultrasound study.

We have previously shown that neonatal high oxygen (O2) exposure in rats leads to hypertension and vascular dysfunction in adulthood. Pulse-wave velocity (PWV), an indirect measure of vascular biophysical properties (arterial stiffness or distensibility), is a sensitive marker of cardiovascular health. Its measurement in rats is mostly based on invasive hemodynamics measurements, prohibiting longitudinal studies particularly relevant in models of developmental programming of cardiovascular dysfunctions. With this study, we sought (1) to verify the feasibility and validity of measuring of aortic PWV in Sprague-Dawley rats by ultrasound; (2) to use the technique to compare aortic PWV in adult rats exposed to O2 as newborns (80% day 3-10 of life) v. controls; and (3) to develop an algorithm to calculate PWV in a non-invasive manner. We calculated aortic PWV using standard echocardiography and electrocardiogram, and validated the measures with PWV obtained by intraaortic catheters. Aortic full length was measured at sacrifice. PWV was significantly increased in O2 exposed (505 ± 18 cm/s) v. control animals (421 ± 17 cm/s, P < 0.01). With regard to weight, femur length and distance from the manubrium to the anal margin (MA length), the latter showed the best correlation (R = 0.84, P < 0.0001) with full aorta length derived from (L) = 0.339 × (MA length) + 4.281. The current data using echo-Doppler method demonstrated increased aortic stiffness in adult rats exposed to hyperoxia as newborns and suggests that non-invasive longitudinal studies of aortic PWV can be performed using the proposed algorithm for estimation of the full aorta length.

Factors important in arterial narrowing.

BACKGROUND: Vascular narrowing in hypertension presents conflicting hypotheses about structural narrowing, vasconstriction, volume expansion, contractile function and other issues more obvious to the physiologist than the cell biologist. Even the cell biology in the injured large arteries used to study atherosclerosis is surprisingly complex. The key issue is that changes in mass, here mainly intimal mass or atherosclerotic plaque, correlate poorly with loss of lumen caliber. An analogy to remodeling of microvessels begs the issue of mechanism. RECENT STUDIES: To explore this, we have focused on two issues: cell death and intramural coagulation. It is likely that cell death, along with tissue factor, promotes coagulation and, in previously injured vessels, fibrin forms in the wall after a repeat injury. In vitro, fibrin promotes smooth muscle gel contraction mediated by an as yet unidentified beta 1 integrin. In vivo, inhibition of coagulation not only prevents vascular narrowing after a reinjury, but may even result in dilation. HYPOTHESIS: We suggest that injury responses, that is, classical wound contracture mechanisms, can be explained as potential pathways for pathologic vascular remodeling.

The time window of apoptosis: a new component in the therapeutic strategy for cardiovascular remodeling.

APOPTOSIS AND EXPERIMENTAL HYPERTROPHY: Apoptosis (programmed cell death) is a physiological counterpart of cell replication with shared as well as specific pathways. Our initial studies have demonstrated increased apoptosis in the heart, kidney and brain of spontaneously hypertensive rats (SHR) and mice, persisting in cultured vascular smooth muscle cells. In these target organs of hypertension, programmed cell death paralleled the well known hypertrophy/hyperplasia. We also observed that the two processes can be dissociated in time, as in experimental hypertrophy of the heart induced by pressure overload. In this context, only a short-lived apoptotic window precedes the overt development of cardiac hypertrophy. EFFECTS IN HYPERTENSION: We now propose that a more prolonged apoptotic window is present in hypertension. Apoptosis seems to be significantly reduced during the first weeks of life in SHR, possibly contributing to the early cardiac hyperplasia. However, increased apoptosis is clearly evident thereafter throughout the development of hypertension and fades below the levels observed in normotensive animals after the age of 24 weeks. ANTIHYPERTENSIVE THERAPY AND APOPTOSIS: In addition to the apoptotic windows that suggest a dynamic regulation of this process in disease states, antihypertensive therapy with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium channel blockers can also modify the contribution of apoptosis, independently of the blood pressure fall. We propose that the presence of apoptotic windows and the involvement of this biological process as a primary or secondary event in cardiovascular remodeling should be taken into account when designing innovative therapeutic approaches.