Heparin inhibits mesenteric vascular hypertrophy in angiotensin II-infusion hypertension in rats.

OBJECTIVE: Chronic infusion with angiotensin II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart and vessels. In order to better understand mechanisms of angiotensin II induced vascular hypertrophy, this study aimed to determine whether heparin, a potent inhibitor of smooth muscle proliferation mechanisms, was able to inhibit vascular hypertrophy. METHODS: Angiotensin II (100, 200 or 300 ng/min/kg s.c.) or a saline vehicle control were infused into rats for 14 days. A separate group of animals were co-infused with heparin (0.3 mg/h/kg i.v.) and angiotensin II (200 ng/min/kg s.c.) to test whether hypertension or hypertrophy were antagonized. Blood pressure was measured by tail cuff method and vessel media cross sectional area was measured by morphometry in aorta and mesenteric arteries. RESULTS: Blood pressure elevation and cardiovascular hypertrophy produced by angiotensin II were strongly dose-dependent. Hypertrophy responses at 14 days of treatment also appeared to be influenced partly by local factors as medial cross sectional area was increased more in mesenteric arteries than in thoracic aorta, and left ventricle weight was least affected. Heparin treatment did not influence the increase of blood pressure in angiotensin II infused animals, but the mesenteric vascular hypertrophy response due to angiotensin II was inhibited by approximately 50%. Inhibition of a modest cardiac hypertrophy and aortic medial hypertrophy did not reach significance. CONCLUSIONS: Angiotensin II infusion produced vascular medial hypertrophy and increased blood pressure, however the inhibitory effect of heparin on hypertrophy in mesenteric arteries was not mediated through angiotensin II induced vasoconstriction or blood pressure elevation. These data suggest that heparin interferes directly with the hypertrophy mechanism in mesenteric arteries, and that heparin-sensitive growth mechanisms are important in mediating angiotensin induced mesenteric vascular hypertrophy.

The type, origin and function of the odontogenic cells of continuously growing guinea-pig molars.

Little is known about which cell types act as the origin of odontogenic stem cells and how these stem cells differentiate to become functional. In the present study 3-day-old guinea-pigs were injected with tritiated thymidine, killed at intervals and their molars studied. The odontogenic cells were found to originate from the stem cells which by autoradiography were shown to be slow cycling and lightly labelled. As they differentiated they became heavily labelled and were designated transit 'dividing cells'. With further differentiation the cells were unlabelled and were designated 'simple transit cells'. It was concluded from the present study that outer enamel epithelium functioned as the source of all odontogenic epithelium; that primitive mesenchyme around the cervical loop functioned as the source of all odontogenic mesenchyme and that all of the transit cells which differentiated to become functional migrated coronally.

Basal cell nuclear size in experimental oral mucosal carcinogenesis.

It has been suggested that the size of the nuclei of epithelial basal cells can be used in predicting the likelihood of malignant transformation of epithelium. This proposition was assessed in rat palatal epithelium after the carcinogen 4-nitroquinoline-1-oxide had been applied to the epithelium for varying periods of time. No consistent alterations in basal cell nuclear size, including area, perimeter, diameter and regularity of form were found with routine light microscopy as the epithelium passed through various stages of dysplasia to carcinoma. This finding casts doubt on the value of using a variation of basal cell nuclear size as a predictor of malignant transformation.

An estimation of ameloblast generation time and of the ameloblast proliferative compartment of guinea pig teeth.

The generation time of inner enamel epithelial cells has been estimated by many investigators using rodent and lagomorph teeth but the results have varied. In the present study of guinea pig molars, the inner enamel epithelial cell generation time (Tc) and its fractions (Ts, Tg2, Tm and Tg1) were calculated. Previous investigators have attempted to determine the extent of the proliferative compartment of inner enamel epithelial cells using the position of mitotic figures as their guide, but results have been inconsistent. It appears that this has been due to the small percentage of mitotic figures among the cell population and the difficulty of visualising them. In the present study, a novel approach was used to determine the extent of the inner enamel epithelial cell proliferative compartment which was not based on the position of mitotic figures, but on the calculation of other generation time fractions. It was found that the proliferative compartment extended for approximately 47 cells occlusally from the synthetic compartment. The results also showed that there was no evidence of stem cells in the ameloblast columns and hence, ameloblasts depended on their cell supply from the stem cell compartment apical to the ameloblast columns.

On the pattern of ameloblast migration.

The kinetics of ameloblast cells in continuously growing guinea pig molars were studied using autoradiography. The results showed that there was no direct relationship between ameloblast migration rate and ameloblast production rate, which indicated that ameloblasts actively migrated coronally. It was found that ameloblast migration rate was maximal at the root apex, and then reduced to a minimum value as the ameloblasts left their proliferative compartment and migrated coronally. A multiple regression model was found to be the most suitable one to represent the ameloblast migration pattern.