Toshimi Kanbe

Studies of hypertension-induced vascular hypertrophy in cultured smooth muscle cells from spontaneously hypertensive rats.

Mechanisms of vascular hypertrophy induced by hypertension were studied in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with those from normotensive Wistar-Kyoto (WKY) rats. Fetal calf serum-stimulated ornithine decarboxylase (ODC) activity of cultured smooth muscle cells was greater in SHR and SHRSP than in WKY. Beta- but not alpha-adrenergic agonist stimulated ODC activity acutely in cultured smooth muscle cells from WKY, and isoprenaline-induced activation was blocked by the beta-blocker, propranolol, and enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. These results indicate that cultured vascular smooth muscle cells from SHR and SHRSP are more prone to increase the protein synthesis than those from WKY through the trophic induction of ODC activity and that the regulation of ODC activity by catecholamines is mediated through beta-agonistic effect in cultured smooth muscle cells.

Genetic Markers in Spontaneously Hypertensive Rats

Establishment of various models for hypertensive diseases such as spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) clarified the importance of genetic factors in the pathogenesis of these diseases and further accelerated studies on their genetic mechanisms. Although various biochemical abnormalities have been detected and can be used as biochemical markers in these models, they have not been always closely related to blood pressure in F2 generation obtained by cross breeding between SHR and normotensive Wistar-Kyoto rats. Recent studies indicate that biomembrane abnormalities detected in erythrocytes and other membranes of SHR and SHRSP may not only be biochemical markers but also related to the pathogenesis of hypertensive diseases.

Enhanced growth rate of cultured smooth muscle cells from spontaneously hypertensive rats

SummarySmooth muscle cells were isolated and cultured from the aortic media of age-matched, stroke-prone and stroke-resistant spontaneously hypertensive rats (SHRSP, SHRSR: SHRs) and Wistar-Kyoto rats (WKY), and the growth rate of cells from the three strains was compared. Under electron microscopical observation the cells were identified as modified (or synthetic-type) smooth muscle cells. Cells occurring at low densities showed the same morphology for both SHRs and WKY, but cells occurring at higher densities were observed to be smaller in SHRs than in WKY. An analysis of the growth curves of cells showed a significantly enhanced replication rate in cells from SHRs compared with those from WKY, especially in the early passages. In later passages (repeated until the 9th passage), however, this distinction was not clear. These growth characteristics were also confirmed in cells from both 12- and 24-week-old, age-matched SHRs and WKY. We could not find any difference between the growth characteristics of cells from SHRSP and SHRSR. It is possible to hypothesize from these findings that the abnormality relating to hypertension (hypertension being a common characteristic of SHRSR and SHRSP) is found in the smooth muscle cells, and is reflected as an enhanced growth rate when they are exposed to mitogenic stimuli, such as in atherosclerosis.

Biomembrane Abnormalities in Spontaneous Hypertension

Recent studies on spontaneously hypertensive rats (SHR) [1] and strokeprone SHR (SHRSP) [2] have brought us both good news and bad news [3]. The bad news is that hypertension and stroke are definitely determined by genetic factors [4]. On the other hand, the good news is that hypertension and stroke can be prevented by modifying environmental factors or by preventive treatments, even if genetic predisposition is strong [3, 5, 6].