ALTERATIONS IN BETA-ADRENOCEPTORS AND POLYPLOIDY IN CULTURED AORTIC SMOOTH-MUSCLE CELLS FROM DIFFERENT AGE-GROUPS OF SPONTANEOUSLY HYPERTENSIVE RATS AND WISTAR-KYOTO RATS

Objective: The relationship between the number of beta-adrenoceptors a nd polyploidy in cultured aortic smooth muscle cells derived from diff erent age groups of spontaneously hypertensive rats (SHR) and normoten sive Wistar-Kyoto (WKY) rats were examined. Design: The number of beta -adrenoceptors, the percentage of multinucleated cells and the inciden ce of polyploidy from cultured smooth muscle cel Is derived from SHR a nd WKY rats aged 3-4, 10-12 and 28-30 weeks were measured. The effect of passaging of the cells on the expression of beta-adrenoceptors and polyploidy on cultured smooth muscle cells from both SHR and WKY rats was also investigated. Methods: Receptor binding experiments were carr ied out using [(125)]-mono-iodocyanopindolol with osmotically lysed cu ltured aortic smooth muscle cells to investigate the properties of vas cular beta-adrenoceptors in SHR and WKY rats. The proportion of polypl oid smooth muscle cells was determined by frequency distribution analy ses of Feulgen DNA microdensitometric measurements. Results: The incid ence of polyploid smooth muscle cells was consistently higher in cells cultured from SHR than in those from WKY rats in all three age groups , with a positive correlation between polyploidy and age in SHR. Furth ermore, in all three age groups the number of beta-adrenoceptor bindin g sites was also higher in cultured smooth muscle cells from SHR than in those from WKY rats. There was no significant difference in the rec eptor affinity. The increase in beta-adrenoceptor number was associate d with an increase in polyploidy, and both of these changes were posit ively correlated both with the age of the rats from which these cells were derived and with the number of passages. Conclusions: Under cell culture conditions the expression of beta-adrenoceptor density increas es with the number of passages in both SHR and WKY rats. Smooth muscle cells derived from older SHR and WKY rats have a greater propensity t o develop polyploidy. This trend is significantly accelerated in cultu red smooth muscle-cells derived from SHR compared with those from WKY rats, suggesting a premature ageing process. These findings suggest th at, in cultured smooth muscle cells from SHR and WKY rats, beta-adreno ceptors may influence the expression of polyploidy.