The consequences of hypertension and aging on cardiovascular structure and function are reputed to be similar, suggesting that blood pressure plays a role in the aging process. However, the exact relationship between aging, blood pressure, and the arterial structure-function relationship has not been demonstrated. To test the effects of aging, renin-angiotensin system, and pressure on the arterial wall, 20 normotensive male WAG/Rij rats were killed at 6, 12, 24, and 30 mo of age and compared with similar groups treated with an angiotensin (ANG)-converting enzyme inhibitor (ACEI), perindopril. Arterial function was determined by a systemic hemodynamic study and by in situ measurement of carotid compliance. Arterial wall structure was determined by histomorphometric and biochemical methods. Aging did not significantly modify blood pressure, but ACE inhibition decreased blood pressure significantly from 6 to 30 mo. Plasma renin activity decreased with age and increased with ACEI. Plasma atrial natriuretic factor increased with age and was significantly decreased with ACEI. Absolute and relative left ventricular weight increased with age, and ACEI delayed these increases. Arterial wall stiffness increased with age, as shown by a significant decrease in systemic and local arterial compliance and by an increase in aortic characteristic impedance. The increase in carotid wall compliance after poisoning of smooth muscle contractile function (KCN) was greater in young (6- and 12-mo old) than in old (24- and 30-mo old) rats. Chronic ACEI treatment increased basal carotid compliance values slightly and did not change KCN carotid compliance. The aortic and carotid luminal size increased regularly with age. Aging was associated without any change in absolute elastin content. In contrast, collagen content increased with aging. Aging was also associated with an increase in medial thickness. Medial thickening was mainly due to smooth muscle hypertrophy. Aging was associated with intimal proliferation, which became progressively thicker and collagen rich. ACEI treatment did not prevent aortic lumen enlargement but significantly postponed the increase in medial and intimal thickening. Biochemical determinations of the aortic wall components confirmed the morphometric data. In conclusion, the age-dependent large artery enlargement and stiffening were observed both in normotensive rats and in those rats whose blood pressure was lowered by ACEI. This suggests that aging and blood pressure affect arterial wall structure and function by different mechanisms.

Cardiac output, blood pressure, and the characteristics of diastolic pressure decay were studied in 12 normal subjects and 23 sustained hypertensive patients of the same age. In normal subjects and in hypertensives, analysis of the diastolic decay showed that i) the form of the decay approximated a simple monoexponential curve during the last two-thirds of the diastolic segment, and ii) the time constant (t) of the curve was positively correlated with the total peripheral resistance (TPR), with an intercept of nearly zero. The validity of the relationship t = K x TPR was demonstrated both in groups of patients and also in individuals. Using a simple model for the vascular system, the K value was identified as the large arteries compliance and could thus be calculated in each individual. The values of arterial compliance was 1.26 +/- 0.04 ml.mmHg-1.m-2 in normal subjects and was significantly reduced in hypertensive patients (0.88 +/- 0.02 ml.mmHg=1.m-2,. P less than 0.001).

Activation of atrial natriuretic factor (ANF) gene expression has been reported in the rat ventricle in several models of hemodynamic overload, including hypertension. However, nothing is known about the potential trigger(s) and the time course of this activation during the development of hypertension. We measured aortic blood pressure, left ventricular hypertrophy (LVH), and left ventricular ANF mRNA concentration (LV ANF mRNA) in a first group of rats (study A) killed at 5 and 18 h and 2, 4, 6, 9, 15, and 30 days after suprarenal coarctation of the abdominal aorta. Coarctation induced a progressive rise in aortic blood pressure and left ventricular mass. We observed a biphasic accumulation of ANF mRNA in the left ventricle with a peak at day 4 averaging 20 times the control value long before stable hypertension and hypertrophy were achieved, followed by a decrease until day 9. This decrease was followed by a new rise, which stabilized around 10 times the control value seen during stable hypertension and hypertrophy. In a second group of rats killed at days 4 and 30 (study B), we determined, in addition to the previous parameters, left ventricular end-diastolic pressure (LVEDP), plasma renin (PRC), and plasma ANF concentrations. LVEDP and PRC were markedly increased at day 4, but at day 30, during stable hypertension and hypertrophy, these parameters returned to control values, whereas plasma ANF was increased. Using immunocytochemistry, we looked in a third group of rats (study C) for the presence of the immunoreactive peptide at days 4 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)

In humans, aging produces many structural changes in blood vessels, one of the most pronounced being arterial calcium overload. Simultaneously arteries become increasingly rigid. The slow evolution of the two processes renders it difficult to evaluate the importance of vascular calcium overload in the development of decreased compliance. To gain insight into this relationship, rapid vascular calcium overload was produced by treating young rats with vitamin D3 and nicotine. When rats were allowed 16 days or longer to recover from such treatment, analysis of plasma parameters revealed no overt toxicity, and growth rate was similar to that of controls. Pronounced calcium overload was seen primarily in compliance arteries. Changes in systemic arterial compliance, characteristic impedance, pulse-wave velocity, and carotid compliance all reflected a substantial increase in arterial rigidity. Linear regression analysis revealed significant correlations between the various indicators of arterial distensibility and arterial calcium content. In conclusion, treatment of young rats with vitamin D3 and nicotine may provide a suitable model with which to investigate how calcium overload is involved in the induration of compliance arteries.