Smooth muscle cell hypertrophy versus hyperplasia in hypertension.

Abstract

Arteries of hypertensive animals have a greater mass of smooth muscle than those of normotensive controls. We examined the contributions ofsmooth muscle cell hypertrophy and hyperplasia to this increase in mass. Cell size measurements obtained by (i) image analysis of enzyme-dispersed cells, (ii) morphometric evaluation of tissue sections, and (iU) biochemical measures of protein/cell and actin/cell ratios on isolated cells showed that average cell size was greater in spontaneously hypertensive rats than in normotensive Wistar-Kyoto and Sprague-Dawley controls. Average DNA/cell ratios were also increased in spontaneously hypertensive rats while protein/DNA ratios were not different. Analysis of nuclear DNA content of individual cells by flow microfluorimetry and Feulgen-DNA microdensitometry measurements showed that >20% of spontaneously hypertensive rat cells were polyploid while <10% of control cells were polyploid. Estimates of cell number per centimeter of aortic length, based on ploidy and DNA content, show no difference between control and hypertensive rats. Thus, smooth muscle hypertrophy alone accounts for the increased mass of smooth muscle in aortas of spontaneously hypertensive rats. Furthermore, this cellular hypertrophy is accompanied by a change in nuclear ploidy. This nuclear response in hypertension may represent a fixed change related to the establishment of a chronic hypertensive state.Folkow and others have implicated thickening ofresistance vessels in the maintenance of increased peripheral resistance in established hypertension (1)(2)(3)(4)(5). This thickening is due, at least in part, to an increase in smooth muscle cell mass (6, 7). It is unclear, however, whether this is due to an increase in cell size-i. e., hypertrophy-or to an increase in cell number-i.e., hyperplasia. Increased cell number has been inferred from increased numbers of vascular smooth muscle cells labeling with [3H]thymidine (8-12) and from an increase in DNA per unit vessel length (11,12) (14), and the endothelium was removed with a piece of Teflon. Media preparations were used for subsequent isolation of smooth muscle cells and for DNA determinations described elsewhere.Smooth muscle cells were isolated by enzyme dispersion as described by . After digestion, cell suspensions were filtered through 250-gm stainless steel wire mesh to remove tissue debris and undigested tissue. The filtrate was centrifuged (200 x g, 5 min), and the cell pellet was suspended in Ca2+-, Mg2e-free Hanks' buffer/0.5 mM ethylene glycol bis(f-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Following incubation for 15-20 min at 370C, cells were fixed (2% glutaraldehyde/1% paraformaldehyde in phosphate buffer, pH 7.0) overnight. Cell viability was >90% as measured by trypan blue exclusion. Cellular yield, determined by DNA assay, was =20% with the greatest loss occurring during the filtration step.For sizing of isolated cells, cell smears of fixed cells were air dried and stained with hematoxylin/eosin. Area measurements (Am2) were ...

Cellular hypertrophy in mesenteric resistance vessels from renal hypertensive rats.

“…6 When the same morphometric method was used, it was found that the medial hypertrophy seen in SHR most likely was caused by hyperplasia. This finding was in agreement with another study 3 on mesenteric vessels of the SHR and also with findings in the genetically hypertensive Dahl strain rat. 27 In contrast to these results, the increased mass of smooth muscle seen in aortas of SHR, 3 4 -» RHR, 14 and other experimental models of hypertension 29 is, with different morphometrical methods, consistently found to be caused by hypertrophy and not hyperplasia.…”

Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy.

“…RT Recent study (45) showed that a low concentration (4.2 pM) of PDGF-AA had mitogenic activity for cultured VSMCs. A recent report (12) showed that biological activity of (40) and levels of some transcription factors such as Egr-l in VSMCs were equivalent in the two strains in the present study, it is unlikely that these approximately twofold increases in Spl and AP-2 in VSMCs of SHRs were caused simply by nonspecific increases in protein synthesis. Furthermore, we found that after lowering of blood pressure by antihypertensive treatment, Spl level in VSMCs of SHRs was also decreased, although AP-2 level was not.…”

NFATc3 Mediates Chronic Hypoxia-induced Pulmonary Arterial Remodeling with α-Actin Up-regulation

“…This activation is mediated by calcineurin and is dependent on both sarcoplasmic reticulum Ca 2ϩ release through inositol trisphosphate receptors (IP 3 R) and extracellular Ca 2ϩ influx through voltagedependent Ca 2ϩ channels (VDCC) (31). Interestingly, during CH, PASMC exhibit increased expression of SM-␣-actin (33,34) consistent with PASMC hypertrophy and vascular remodeling (35). In addition, it has been shown that Ang II, which is elevated during CH (36 -38), induces stimulation of SM-␣-actin expression at the transcriptional level through a SRF-dependent mechanism in cultured VSMC (36 -39).…”