This study was designed to determine the effects of angiotensin II infusion on structure of conduit and resistance arteries and to see if the effects correlate with changes in platelet-derived growth factor A chain (PDGF-A) gene and protein expression. Wistar rats were subcutaneously infused by osmotic minipump with either angiotensin II (ANG II) at 200 ng.kg-1.min-1 or physiological saline (control) for 14 days. Tail-cuff systolic blood pressure was significantly higher in ANG II compared with control rats beginning the second day of infusion and continuing to the end of 2 wk. Both aorta and external spermatic artery (first-order arteriole of the cremaster muscle) developed increased wall-to-lumen ratios in the ANG II rats, but this occurred by hypertrophy of the wall in the aorta and reduction of the lumen in the arteriole. Digoxigenin-labeled cRNA probes were used for in situ hybridization of vascular sections to identify PDGF-A mRNA. Gene expression of PDGF-A in ANG II rats was upregulated in the hypertrophied aorta and the nonhypertrophied arteriole. With the use of immunocytochemistry techniques, PDGF-A and proliferating cell nuclear antigen were increased in the aorta but not in the arterioles of ANG II rats compared with control rats. These results suggest that the difference in growth response between the aorta and the arteriole induced by ANG II may lie in posttranscriptional modification of PDGF-A mRNA, differential control of transition, or turnover of PDGF-A protein.

Results from studies using pump-perfused rat hindquarters are consistent with increased wall-to-lumen ratios in resistance vessels of spontaneously hypertensive rats (SHR). However, in vivo measurements of cremaster arterioles have not shown increased wall-to-lumen ratios in SHR. To investigate this discrepancy, we studied three groups of male SHR and Wistar-Kyoto rats at 12 weeks of age. In the first two groups, the cremaster muscle was prepared to allow microscopic observation while the hindquarters were pump-perfused with increasing concentrations of norepinephrine in oxygenated Tyrode's solution. Both groups of SHR showed an increase in vasodilated resistance and elevated maximal vasoconstrictor response. In the first group, arterioles showed dose-dependent constriction that was greater in smaller arterioles but did not differ between hypertensive and normotensive rats. Vasodilated diameters of second-order arterioles were significantly smaller in the hypertensive rats. In the second group, servo-null pressures in the first-order arteriole showed that the microvessels contributed proportionally to the elevation in resistance in both SHR and normotensive rats. In the third group, first- and second-order arterioles were measured in vivo and histologically. Arteriolar diameters did not differ between SHR and normotensive rats with either method. In fixed sections the cross-sectional area of the media-intima was greater in the SHR. Therefore, data from the pump-perfused rat hindquarters accurately reflect vasoconstrictor responses of the arterioles, and in deference to in vivo measurements on arteriolar walls that include the adventitia, the increased response in the SHR can be explained by hypertrophy of the arteriolar medial-intimal area.

Adaptive responses of mature arterioles were examined after a 38% reduction in total blood flow to the cremaster muscle produced by unilateral orchidectomy in 12-wk-old rats. Four weeks later, the muscle was smaller than the contralateral cremaster, which did not increase in size during this period. Measured by closed-circuit television microscopy, the internal diameters of first- through fourth-order arterioles (1A-4A) were smaller, but wall cross-sectional area was reduced only in 3As. The smaller diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. As determined from the perfusion-fixed, microfilled cremaster muscles, the total length of the arcading arterioles and the number of 3As were not statistically different, but the total number of 4As was significantly reduced on the orchidectomy side. Therefore, chronic load reduction in a mature muscle resulted in reduced blood flow, decreased number of 4As, and smaller arteriolar internal diameters in the absence of net changes in vascular wall cross-sectional area. A local autoregulatory mechanism related to flow-induced shear stress is suggested as the mechanism mediating the changes.

The purpose of this study was to evaluate acute and chronic autoregulation of blood flow in the cremaster muscle of one-kidney, one-clip (1K1C) hypertensive rats and to investigate alterations of shear stress during the development of hypertension. Unilateral renal artery stenosis and contralateral nephrectomy were performed in half of the rats and a sham operation was carried out in the other half. Mean blood pressure was significantly increased at 1 (38%) and 4 (34%) weeks in 1K1C rats v age-matched controls. Heart rate was significantly increased 15% at 1 week in 1K1C rats but returned to the control level at 4 weeks. Cremaster arteriolar dimensions were measured in vivo by intravital microscopy. Resting diameter of the first-order arteriole (1A) in 1K1C rats was decreased by 25% (P < .05) at 1 week and by 16% at 4 weeks (ns). Measured by the dual-slit technique, total blood flow to the cremaster muscle in 1K1C rats was reduced by 58% (P < .05) at 1 week but was not significantly different from control at 4 weeks. Wall shear rate calculated in the 1A of 1K1C rats was not significantly different from control at 1 week but was elevated 70% (P < .05) at 4 weeks. Therefore, autoregulation of blood flow in skeletal muscle is impaired and/or overridden in the acute phase of 1K1C hypertension. Shear rate, however, did not deviate from the control level until later, which might be the result of impaired function of the endothelium in chronic hypertension.

To explore the effect of chronic converting enzyme inhibition on the macro- and microcirculation, normotensive rats were chronically given 100 mg/kg/day of captopril in their drinking water beginning one day before uninephrectomy. Cremaster arteriolar dimensions were measured 2, 4, or 8 weeks later by intravital microscopy, before and after topical application of 10(-3) M adenosine. Mean blood pressure were significantly decreased at 4 (17%) and 8 (18%) weeks in treated rats vs age-matched control. Structural diameter reductions occurred in large arterioles starting 4 weeks in treated rats, and in small arterioles at 8 weeks. The cross-sectional wall area of large arterioles increased with age in control animal, but not in captopril treated one. Eight weeks of captopril treatment also decreased the cross-sectional wall area in small arterioles. Measured by stereological techniques, small arteriolar density decreased 17% at 4 weeks and 13% at 8 weeks in treated rats. Using histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in treated rats at 4 (24%) and 8 (15%) weeks without a significant change in internal diameter.

The purpose of this study was to evaluate microvascular development during normal skeletal muscle maturation and to determine the alterations associated with decreased blood flow caused by a decrease in demand. Unilateral orchidectomy was performed on 4-wk-old rats to reduce muscle tension and growth of one cremaster muscle. Three weeks later, total blood flow was reduced to 58 +/- 9% measured by the dual-slit velocity technique and 55 +/- 9% by radioactive microspheres, and the muscle was smaller when compared with the intact contralateral muscle. Blood flow per gram of tissue was not significantly different. Measured by closed-circuit television microscopy, the internal diameters and wall cross-sectional areas of all orders of arterioles (1A-4A), and the number of 4As per 3A had increased with age in the control muscle. The arcading arterioles increased in length by 35% as the intact muscle grew, but the number of 3As remained unchanged. Arteriolar length increased but not in proportion to muscle mass. As a result, large and small arteriolar density decreased with age. Thus, during normal skeletal muscle maturation, preexisting arterioles became elongated and only precapillary arterioles increased in number, resulting in a decreased ratio of arteriolar number to tissue mass. Unilateral orchidectomy inhibited the growth of arterioles in both size and number. A reduced diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. Flow-induced shear stress and/or local changes in growth factors are suggested as possible mechanisms mediating the alterations.

This experiment was designed to investigate the effect of converting enzyme inhibition on functional and structural vascular alterations in one-kidney, one clip hypertensive rats and in normotensive rats. Starting 1 day before surgery, 100 mg/kg/day captopril was given chronically to half of the hypertensive and normotensive groups in their drinking water. With use of intravital microscopy in the cremaster muscle, arteriolar dimensions were measured 4 weeks later, both before and after topical application of 10(-3) M adenosine. Mean blood pressure was 124 +/- 4 mm Hg in control rats and 103 +/- 5 mm Hg in captopril-treated control rats (p less than 0.05). Mean blood pressure was significantly elevated to 183 +/- 5 mm Hg in captopril-treated one-kidney, one clip hypertensive rats and 193 +/- 5 mm Hg in one-kidney, one clip hypertensive rats. With use of histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in captopril-treated control rats (24%), and hypertrophy of the aortic wall in one-kidney, one clip hypertensive rats was decreased 26% by captopril. Structural diameter reductions occurred in large arterioles of the captopril-treated control and hypertensive groups and the nontreated hypertensive group. In spite of a significant increase in wall-to-lumen ratio of first-order arterioles in all captopril-treated rats, captopril decreased cross-sectional wall area of these vessels 37% in hypertensive and 20% in control rats, respectively. Measured by stereological techniques, small arteriolar density decreased 30% in captopril-treated hypertensive rats and 17% in captopril-treated control rats. Therefore, smaller arteriolar lumens, decreased aortic and arteriolar cross-sectional wall area, and arteriolar rarefaction after converting enzyme inhibition, in spite of rising or falling blood pressure, are evidence that vascular growth was inhibited in vivo.