Abstract-Angiotensin II (Ang II) may induce arterial hypertrophy either directly or through an increase in arterial pressure. To separate these 2 mechanisms, rats were implanted with osmopumps delivering either Ang II (100 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or saline. 5-Bromo-2Ј-deoxyuridine (BrdU) was delivered to both groups by osmopump (2.5 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ). Half of the rats in each group were given minoxidil (9 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ) in their drinking water. After 14 days, systolic blood pressure was 117Ϯ2, 124Ϯ3, and 115Ϯ2 mm Hg in the control, Ang II-minoxidil, and minoxidil groups, respectively, and 181Ϯ6 mm Hg in the Ang II group (PϽ0.05). After perfusion-fixation, the thoracic aorta, carotid artery, small mesenteric artery, external spermatic artery, and kidneys were harvested, paraffin-embedded, and used for morphological measurements, immunohistochemistry for BrdU, and in situ hybridization with a 35 S-labeled riboprobe for platelet-derived growth factor-A chain (PDGF-A) mRNA. The walls of the aorta and carotid arteries hypertrophied in the Ang II group only. There were no significant morphological differences in the small arteries. BrdU was negative in all arteries but positive in the renal tubules. Expression of PDGF-A was elevated 8-fold in the thoracic aorta of the Ang II group (PϽ0.05). These results show that (1) arterial hypertrophy from Ang II infusion occurs in response to elevated arterial pressure, (2) hypertrophy was not associated with hyperplasia or polyploidy of vascular smooth muscle cells, and (3) PDGF-A expression correlated with elevated pressure and arterial wall hypertrophy. (Hypertension. 1998;32:452-458.) Key Words: pressure Ⅲ angiotensin II Ⅲ hypertrophy Ⅲ growth substances H ypertension is characterized by structural alterations of the vasculature, depending on the size and function of the particular vessel. During the course of hypertension, the larger arteries hypertrophy 1,2 while the lumen diameter of smaller arterioles is reduced without a change in crosssectional wall area.3,4 The lumen reduction in absence of hypertrophy is termed "inward eutrophic remodeling" and was first reported on the submucosal arterioles of the intestine in hypertensive individuals. 5 The small arteries (150 to 250 m ID) are found at the overlap where hypertrophy decreases and eutrophic remodeling begins, wherein they experience either an inward eutrophic or hypertrophic remodeling depending on the type of hypertension. 6,7 Many factors have been proposed to explain the structural alterations that occur during hypertension. One is the hormone angiotensin II (Ang II), which is a hypertrophic and hyperplastic stimulus of vascular smooth muscle cells, 8,9 as well as an inducer of platelet-derived growth factor-A chain (PDGF-A) expression.10 A second factor is elevated intravascular pressure itself. Like Ang II, elevated pressure is also considered a hypertrophic stimulus 2,11,12 and is linked to PDGF-A expression.13 As a consequence of the effect of Ang II on blood pressure, it is often difficult to distinguish...

. AT 1 receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension. Am. J. Physiol. Heart Circ. Physiol. 278: H613-H622, 2000.-To separate the role of ANG II from pressure in hypertrophy of the vascular wall in one-kidney, one-clip (1K1C) hypertension, experimental and shamoperated rats were given the AT 1 -receptor antagonist losartan (20 mg · kg Ϫ1 · day Ϫ1 ) or tap water for 14 days. Mean arterial pressure was elevated in both experimental groups compared with controls. Rats were anesthetized with pentobarbital sodium, and the thoracic aorta and carotid, small mesenteric, and external spermatic arteries were harvested and embedded in paraffin. Tissue sections were used for morphological analysis, immunohistochemistry for 5-bromo-2Ј-deoxyuridine (BrdU) and platelet-derived growth factor (PDGF)-AA, stereological measurements, and in situ hybridization with a 35 S-labeled riboprobe for PDGF-A mRNA. Elevated cross-sectional areas of thoracic, carotid, and small mesenteric artery in 1K1C rats were not reduced by losartan. The internal diameter of the external spermatic artery and microvascular density of the cremaster muscle were reduced in 1K1C rats. The number of BrdU-positive nuclei per cross section did not differ between 1K1C and control arteries. PDGF-A mRNA was elevated in the arterial walls of 1K1C rats compared with controls and was hardly changed by losartan. PDGF-A protein stained strongly in the media of 1K1C arteries and was not inhibited by losartan; it appeared in the adventitia of all aortas and carotid arteries. These observations demonstrate that effects of ANG II mediated through the AT 1 receptor are not necessary for hypertrophy of the vascular wall during 1K1C hypertension or expression of PDGF-A.one-kidney, one-clip hypertension; losartan; arterial pressure; angiotensin; platelet-derived growth factor DURING THE COURSE of hypertension, individual arteries adapt to mechanical and hormonal stresses through alterations in medial thickness and/or internal and external diameters, depending on the size and function of the particular blood vessel. The larger arteries increase wall cross-sectional area with the development of outward hypertrophy (30, 45). The smaller arterioles undergo a decrease in lumen size without an increase in wall area and/or rarefaction, the reduction in number of functional vessels (16,31,38). Lumen reduction in the absence of hypertrophy is termed ''inward, eutrophic remodeling.'' Both ANG II and pressure have been implicated as stimuli for the vascular changes associated with hypertension (4,9,18,30,45). ANG II is a hypertrophic (18) as well as hyperplastic stimulus (47) of vascular smooth muscle cells (VSMCs) and has been shown to induce platelet-derived growth factor (PDGF)-A chain expression (28). Recently, we have shown that vascular hypertrophy following chronic infusion of ANG II was entirely prevented when the blood pressure was kept from rising by the simultaneous administration of minoxidil (34). Pressure, like ANG II,...

No abstract