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Systemic arterial elastic properties, important determinants of left ventricular function and coronary blood flow, are compromised in myocardial infarction (MI). The cardiac effect of angiotensin-converting enzyme inhibitors (ACEIs) has been extensively studied, whereas their arterial effect has been poorly reported in MI. The aim of this work was to study the effect of prolonged ACEI enalapril treatment on systemic arterial structure and elastic properties in rats with MI. One week after the induction of an MI, 40 male Wistar rats received either no treatment (n = 20) or ACEI enalapril (2 mg/kg; n = 20) for 17 weeks. At the end of the treatment period, blood pressure, cardiac output, total peripheral resistance, systemic arterial compliance, characteristic impedance, and left ventricular power were measured in anesthetized rats. Then the rats were killed for infarct-size determination and aortic histomorphometric study. Infarct size, heart, and left and right ventricular weights were similar in the ACEI-treated and untreated infarcted rats. Prolonged ACEI enalapril treatment reduced blood pressure by 17% (p < 0.001), total peripheral resistance by 22% (p < 0.01), and characteristic impedance by 26% (p < 0.03), and increased systemic arterial compliance by 35% (p < 0.01), in comparison with untreated infarcted rats. Enalapril reduced aortic media wall thickness by 9% (p < 0.02) and increased elastin content by 22% (p < 0.03) and elastin-to-collagen content ratio by 42% (p < 0.01). Enalapril did not affect cardiac output and left ventricular power. Smooth muscle cell nuclei number and size and collagen content of aortic wall were similar in the ACEI-treated and untreated infarcted rats. These results indicate that long-term treatment with ACEI enalapril improves arterial elastic properties through structural modifications of arterial wall in rats with MI. This vascular effect may contribute to improve the left ventricular function and the coronary perfusion of infarcted myocardium, and added to the cardiac effect, may explain the prevention of left ventricular remodeling observed with ACEI in this model.

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.

The effects of long-term angiotensin-converting enzyme (ACE) inhibitor treatment with perindopril 2 mg/kg/day, by gavage, for 3 months on the mechanical function and structure of large arteries were studied in adult spontaneously hypertensive rats with established hypertension. Hemodynamic parameters, including instantaneous aortic blood flow and pressure, were recorded under anesthesia at the end of the treatment period. Systemic arterial compliance was calculated from aortic pressure and flow recordings; passive mechanical properties of the in situ localized carotid artery were measured. Histologic and morphologic parameters of the aortic media, including cross-sectional area and thickness, size, and density of smooth muscle nuclei and of elastin and collagen fibers, were measured using an automated image analysis system. ACE inhibitor treatment significantly decreased mean arterial pressure (-27%, p < 0.001) and total peripheral resistance (-30%, p < 0.05) while cardiac output was increased (29%, p < 0.05). Systemic arterial compliance and carotid compliance were both increased by treatment (63%, p < 0.05, and 83%, p < 0.05, respectively). Morphometric assessment of vascular structure showed that ACE inhibitor treatment significantly decreased medial cross-sectional area (-36%, p < 0.001) and thickness (-16%, p < 0.001) by affecting smooth muscle cell hypertrophy (nucleus size decreased by 26%, p < 0.05) without changes in smooth cell number. Collagen density was decreased by treatment (-42%, p < 0.05), whereas elastin density was not affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A nonhypotensive dose of atrial natriuretic peptide (ANP) was infused (60 pg/kg body wt per day s.c. by osmotic pump) for 25 days in 16-week-old normotensive Wistar-Kyoto rats (WKYs, n = 12) and age-matched spontaneously hypertensive rats (SHRs, n = 12). During the infusion period, systolic blood pressure, urinary volume, and cyclic guanosine monophosphate (cGMP) excretion/12 hr were measured once a week in both groups. Then mechanical and morphological properties of the arterial wall and plasma ANP levels were assessed and compared with those from control groups of SHRs (n = 8) and WKYs (n = 8) receiving a saline vehicle. The compliance (CC) of the in situ localized carotid artery was measured for pressures ranging from 25 to 175 mm Hg under control conditions and after "poisoning" of smooth muscle tone by potassium cyanide. After pressure fixation, the medial thickness, elastin and collagen contents, and the size and number of nuclei were measured in the thoracic descending aorta. In WKYs, ANP did not modify either mechanical or structural properties of the arterial wall or biochemical parameters. Conversely, in ANP-treated SHRs, CC was significantly increased compared with untreated SHRs under basal conditions (p < 0.03) and after potassium cyanide poisoning (p < 0.02). Structural properties were also modified by ANP in SHRs, i.e., medial thickness (129.3 +/- 4.1 versus 113.1 +/- 3.3 microns, p < 0.01) and nuclear size (8.81 +/- 0.28 versus 5.52 +/- 0.20 microns 2, p < 0.0001) in untreated and treated SHRs, respectively. Furthermore, urinary volume and cGMP content were significantly increased during ANP infusion in treated SHRs (p < 0.05). The present results indicate concomitant modifications of mechanical and structural properties of the arterial wall in SHRs chronically treated with low doses of ANP. These long-term effects of ANP could be involved in the remodeling of the arterial wall observed during hypertension and could have beneficial effects on cardiovascular diseases in chronic sustained hypertension.

The effects of urapidil, a phenylpiperazine substituted derivative of uracil with selective alpha 1-adrenoceptor antagonist properties, on the mechanical properties of the arterial wall in hypertensive rats and male patients were studied. 15 twelve-week-old spontaneously hypertensive rats (SHR) were compared with 15 matched normotensive control Wistar Kyoto rats (WKY), in order to study carotid compliance in opened-chest anaesthetised animals. Carotid compliance was determined from the arterial volume-pressure relationship under control conditions, and after treatment with urapidil. Carotid compliance increased markedly (+31%; p less than 0.01) in WKY after incubation in situ with urapidil at doses corresponding to 0.5 and 1 mg/kg but it did not change significantly in SHR. Incubation with urapidil 2 mg/kg was necessary to induce a marked increase (+38%) in carotid compliance in SHR. In 12 male patients with hypertension who received intravenous urapidil 250 micrograms/kg infused as a single dose, pulse wave velocity decreased slightly (p less than 0.02) but no significant changes occurred in diameter and compliance. The study showed that urapidil influences arterial smooth muscle tone in rats and male patients, with resulting changes in arterial compliance; these changes are more substantial in animals than in humans.

The effect of hypertension and of therapy by converting enzyme inhibitor (S 9490-3, perindopril) on the function and structure of large arteries has been studied in two-kidney, one-clip Goldblatt hypertensive rats. After one month without treatment, clipped hypertensive rats (n = 24) and sham-operated rats (n = 24) were randomly allocated to treatment by S 9490, 1 mg/kg once a day (n = 24) or to placebo (n = 24) and pursued for 4 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity measured by Döppler, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were recorded in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Morphological parameters of the aortic media, including medial thickness, nucleus density, and cross sectional area and relative density in proteins of interstitial matrix, were recorded by an automated morphometrical system. Hypertension was associated with an increase in characteristic impedance of the aorta and a decrease in compliance of the arterial system. Treatment with converting enzyme inhibitors completely reversed these in vivo markers of the rigidity of large arteries. Hypertension was associated with a shift of the passive pressure-volume relation in the carotid. Treatment with converting enzyme inhibitors normalized the carotid pressure-volume relation, whereas poisoning smooth muscle cells induced a disappearance of the curve differences between hypertensive and normotensive animals. Morphometric analysis of aortic walls permits us to report this functional change to structural modification of the arterial wall. Aortic media thickness was increased by hypertension; this phenomenon was reversed by treatment. Modification of aortic thickness was due to hypertrophy of smooth muscle cells with parallel modifications of absolute amount of collagen, whereas absolute amount of elastin did not change in this early phase of renovascular hypertension in young rats. Treatment with converting enzyme inhibitors reversed the thickness of aortic media without regression of the increase in absolute amount of collagen content whereas absolute amount of elastin content did not change.

The effects of chronic therapy, using an angiotensin converting enzyme (ACE) inhibitor (S9490-3 perindopril, 1 mg/kg), on the mechanical and structural properties of large arteries were studied in two-kidney, one clip (2K, 1C) Goldblatt hypertensive and spontaneously hypertensive rats (SHR) compared with matched normotensive Wistar and Wistar-Kyoto (WKY) animals. The treatment was carried out for 1 month in Goldblatt-hypertensive rats and 3 months in SHR, i.e. for 1 month after blood pressure was normalized. At the end of the treatment period the passive mechanical properties of the isolated carotid artery were measured in situ. Carotid compliance was calculated from the pressure-volume relationship between 50 and 250 mmHg. Morphological parameters of the aortic wall, including medial thickness, nucleus density and elastin and collagen content, were recorded by an automated morphometric system. Renal and essential hypertension were associated with a shift of the passive pressure-volume relationship in the carotid, corresponding to a decrease in arterial compliance. The passive mechanical properties of the carotid were normalized by ACE inhibitor treatment in renovascular hypertensive rats but remained unchanged in chronically treated SHR. The ACE inhibitor completely reversed the medial hypertrophy in Goldblatt-hypertensive rats but the reversal of medial hypertrophy was incomplete in SHR. The elastin to collagen ratio in the aortic media was significantly increased by 3 months of treatment with the ACE inhibitor in the SHR and WKY groups but remained unchanged in the Goldblatt-hypertensive and Wistar rats treated for 1 month.

Possible reduction in arterial thickness may be an interesting way to reduce left ventricular afterload in various pathologic conditions. We tested the effects of cicletanine (3 mg/kg) on the systemic hemodynamics and the mechanical properties of the arterial walls in 12-week-old normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The mechanical properties of the arterial walls were assessed using three independent methods: the characteristic impedance of the ascending aorta (Zc), systemic arterial compliance (SAC), and compliance of the carotid artery (CC). Zc and SAC were calculated from phasic records of pressure and flow in the ascending aorta; CC was measured in situ with or without smooth muscle cell activity [potassium cyanide (KCN) poisoning]. After chronic therapy by daily gavage for 15 days, there were no significant changes in either WKY and SRH in terms of arterial blood pressure (BP), cardiac output (CO), and heart rate (HR). In contrast, Zc, SAC, and passive distensibility of the isolated carotid arteries were significantly improved in treated groups. The increase in arterial distensibility reflected modifications in function (smooth muscle tone) of the arterial wall after cicletanine chronic therapy. Although the exact mechanisms of the observed changes in arterial mechanics remain unclear, this study showed that in experimental hypertension cicletanine can affect distensibility of large arteries independently of significant changes in BP.

A decreased compliance of the large arteries is generally associated with hypertension. However, it has not been determined if the increased stiffness of the arterial wall is related to etiology or if it represents the response of the arterial wall to elevated arterial pressure. We attempted to measure the arterial compliance (SAC) and the aortic diameter in 10 normotensive (WKY) rats and 10 spontaneously hypertensive rats (SHR) before and after injection of an alpha-blocker (Nicergoline 2 mg/kg). SAC was calculated from the diastolic decay of the aortic pressure, using a simple Resistance Capacitance model of the arterial system. The end diastolic diameter of the aorta was measured with a macrophotographic method. In basal conditions, SAC was significantly lower in the hypertensive rats (2.25 +/- 0.81 X 10(-3) ml/mm Hg) than in normotensive rats (5.09 +/- 1.29 X 10(-3) ml/mm Hg). The external diameter of the aorta was larger in SHR: 1.61 +/- 0.04 vs. 1.32 +/- 0.13 mm in WKY. After infusion of Nicergoline, there was no significant difference in blood pressure in either strain. SAC increased significantly in SHR and WKY rats (+60 and +43%, respectively), whereas the aortic diameter did not change significantly in either group. These data suggest that (a) the arterial wall has stiffer intrinsic mechanical properties in SHR as compared with WKY rats, and (b) the alpha-blocking agent used produces a more marked smooth muscle relaxation in the arterial wall of SHR as compared with control animals.