ARTERIAL SMOOTH-MUSCLE RESPONSES IN ADULT AND MODERATELY AGED SPONTANEOUSLY HYPERTENSIVE RATS

In order to further clarify differences between spontaneously hyperten sive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats as well as th e effects of ageing, vascular smooth muscle responses of mesenteric ar terial rings and intracellular free calcium concentration ([Ca2+](i)) in platelets and lymphocytes were studied in 20-week-old and 32-week-o ld animals. Arterial contractile responses induced by noradrenaline an d potassium chloride were comparable in 20-week-old SHR and WKY rats, whereas at 32 weeks of age maximal contractile force generation to bot h of these agents was clearly lower in SHR. In both age groups the cal cium entry blocker nifedipine was more effective in inhibiting potassi um chloride-evoked responses in SHR than in WKY rats, and arterial rel axation responses by endothelium-dependent (acetylcholine) and endothe lium-independent (nitroprusside, isoprenaline) mechanisms were more pr onounced in WKY rats when compared with SHR. The ability of vascular s mooth muscle cells to sequester calcium was evaluated by first depleti ng cellular calcium stores with maximal contractions to noradrenaline in calcium-free buffer, whereafter calcium was returned to the organ b ath. After a 10 min. calcium loading period the arterial rings were re challenged with noradrenaline. Both in 20-week-old and 32-week-old rat s these reponses were less marked in SHR than in WKY rats, suggesting reduced ability of smooth muscle cells to sequester calcium. In additi on, platelets and lymphocytes were used as cell models to examine [Ca2 +](i) in the experimental groups by the fluorescent indicator quin-2. In these two cell types [Ca2+](i) was higher in SHR than in WKY rats i n both of the age groups studied. In summary, differences between SHR and WKY rats in cellular calcium handling are expressed as impaired re laxation and reduced sequestration in SHR vascular smooth muscle and a s higher [Ca2+](i) in blood cells. Ageing seems to have clear effect o nly on contractile force generation which is reduced in SHR mesenteric artery both in agonist-mediated and in depolarization-induced respons es.