Do incremental increases in blood pressure elicit neointimal plaques through endothelial injury?

Abstract

Fowl (males more than females) show maturation-dependent rises in blood pressure (BP) and formation of neointimal plaques (NPs), resembling balloon catheter injury-induced neointima, in the abdominal aorta (AbA) just above the bifurcation. The plaque comprises neointimal cells containing abundant endoplasmic reticulum and extracellular matrix. Hence, we investigated whether rapid incremental BP increases in male chicks trigger NP formation, possibly via endothelial injury in hemodynamically selective areas. In 6-wk-old chicks (n ϭ 8) treated 4 wk with solvent (Sv; minipump) or arginine supplement (Arg; 0.3% in drinking water), BP increased from 140 Ϯ 5 to 159 Ϯ 4 (Sv) and from 138 Ϯ 4 to 157 Ϯ 3 (Arg) mmHg, whereas propranolol treatment (Prop, 8 mg⅐kg Ϫ1 ⅐day Ϫ1; minipump) prevented the rise. Arg and Prop groups had, respectively, 73% and 77% smaller (P Ͻ 0.05) NP areas and 19% and 25% less (P Ͻ 0.01) AbA medial thickness than Sv controls. In 16-wk-old cockerels, established BP remained high after Sv and Arg treatments. In the Prop group, BP decreased, but neither NP area nor medial thickness was lower than in the Sv group, whereas the Arg group showed greater NP area and medial thickness. Pulse pressure, determined by intravascular transducer, increased as the pulse wave descended the aorta. The results suggest that maturation-dependent rises in BP in chicks may trigger NP formation in the lower segment of the AbA, which was prevented by inhibition of BP increase, or via a possible increase in nitric oxide availability. BP reduction exerts no effect once BP reaches a plateau. Involvement of endothelial injury leading to NP formation and hemodynamic forces selective for the lesion-prone area remain to be determined. arginine supplement; nitric oxide; hypertension; atherosclerosis; fowl model; pulse pressure; endothelial dysfunction; endothelial nitric oxide synthase uncoupling BIRDS, particularly fowl, have higher blood pressure (BP) than most mammals. In both male and female fowl, BP is already ϳ150 mmHg at 2-3 wk after birth, and at plateau levels, mean BP is higher in males (194 Ϯ 4.6 mmHg) than in females (169 Ϯ 3.1 mmHg) (13,29,30). In males, BP tends to increase with maturation and/or age, whereas an age-dependent change is not clear in females (30). Before sexual maturation, vascular neointimal plaques (NPs), comprising deformed endothelial cells, proliferating neointimal cells of synthetic phenotype, increased endoplasmic reticulum, and abundant extracellular matrix, are spontaneously formed without a high-cholesterol or high-fat diet (30). The NP lesions are seen in the abdominal aorta, most frequently just before the aortic bifurcation into the ischiadic arteries (referred to as the lesion-prone area); the size of the NP area increases with maturation and/or age, whereas vascular smooth muscle (SM) exhibits adaptive hypertrophy (30). In humans, aging and hypertension are major factors in the induction of arterial hardening (6, 28), and increased brachial pulse pressure (PP), aortic pulse wave velocity ...

Pulse wave velocity and age- and gender-dependent aortic wall hardening in fowl

“…Also, we have previously reported age-dependent BP levels in conscious chickens (Fig. 6) (Nishimura et al, 1981, 2001; Kamimura et al, 1995; Ruiz-Feria et al, 2004a,b). …”

“…One segment (~ 3 mm) of abdominal aorta was excised just above the ischiadic artery bifurcation and processed for dehydration and embedding, for histological examination. The aorta was pinned on a board (overnight in fixative), simulating the architectural organization in vivo (Ruiz-Feria et al, 2004a). Cross sectioning and staining (hematoxylin-eosin) were conducted at the Integrative Microscopy Center of the University of Memphis.…”

“…In both male and female chickens, BP starts to rise after birth; and at plateau levels, BP is higher in males (194.0 ± 4.6) than in females (169.3 ± 3.1) (Nishimura et al, 1981; Kamimura et al, 1995; Nishimura et al, 2001; Ruiz-Feria et al, 2004a,b). As early as 6 wk of age in chickens fed a diet that is not high-cholesterol or high-fat, vascular neointimal plaques are frequently seen in the abdominal aorta just above the ischiadic bifurcation, and most frequently on the ventrolateral side (the “lesion-prone” area) and in the branching points (Rymaszewski et al, 1976; Penn et al, 1980; Nishimura et al, 2001; Ruiz-Feria et al, 2004a,b). Spontaneous development of neointimal plaques may be attributed to vascular endothelium injury induced by exposure of the vascular wall to a rapid incremental rise in BP from the low-pressure system of embryonic life (26-29 mm Hg) and the neonatal period (40-60 mm Hg) to the high-pressure system in mature chickens (Nishimura et al, 2001; Ruiz-Feria et al, 2004a,b).…”

“…As early as 6 wk of age in chickens fed a diet that is not high-cholesterol or high-fat, vascular neointimal plaques are frequently seen in the abdominal aorta just above the ischiadic bifurcation, and most frequently on the ventrolateral side (the “lesion-prone” area) and in the branching points (Rymaszewski et al, 1976; Penn et al, 1980; Nishimura et al, 2001; Ruiz-Feria et al, 2004a,b). Spontaneous development of neointimal plaques may be attributed to vascular endothelium injury induced by exposure of the vascular wall to a rapid incremental rise in BP from the low-pressure system of embryonic life (26-29 mm Hg) and the neonatal period (40-60 mm Hg) to the high-pressure system in mature chickens (Nishimura et al, 2001; Ruiz-Feria et al, 2004a,b). Recently, we found that pulse pressure increases along the descending aorta and that this increment is steeper in young adult male chickens, whereas such increases are much smaller in chicks (either sex) and adult females (Ruiz-Feria et al, 2004a,b).…”

“…Spontaneous development of neointimal plaques may be attributed to vascular endothelium injury induced by exposure of the vascular wall to a rapid incremental rise in BP from the low-pressure system of embryonic life (26-29 mm Hg) and the neonatal period (40-60 mm Hg) to the high-pressure system in mature chickens (Nishimura et al, 2001; Ruiz-Feria et al, 2004a,b). Recently, we found that pulse pressure increases along the descending aorta and that this increment is steeper in young adult male chickens, whereas such increases are much smaller in chicks (either sex) and adult females (Ruiz-Feria et al, 2004a,b). In humans, aging and hypertension are major factors that induce arterial hardening and an elevation of pulse pressure and pulse wave velocity (PWV) in the aorta and its major branches (O'Rourke et al, 1968; Rowell et al, 1968).…”