FUNCTIONAL ALTERATIONS IN THE AORTA OF THE SPONTANEOUSLY HYPERTENSIVERAT - PHARMACOLOGICAL ASSESSMENT WITH CYCLOPIAZONIC ACID

One of the changes in vascular smooth muscle membranes associated with hypertension is an alteration in Ca2+ handling. It has been unclear a s to whether changes occurred at the plasma membrane or at the endopla smic reticulum (ER) or both. Recently, cyclopiazonic acid (CPA) has be en reported to inhibit selectively the ER Ca2+ pump. We aimed at deter mining the effect of ER Ca2+ pump inhibition by CPA on the contractili ty of aortic smooth muscle from 4- to 5-month-old SHR and age- and wei ght-matched WKY control rats. The responsiveness of the SHR tissues to phenylephrine or K+ was significantly reduced as compared with contro ls, although the sensitivity was not altered. Stimulation with phenyle phrine (10 mumol/l) in Ca2+-free medium caused a significantly reduced transient contraction in SHR as compared with control tissues. After pretreatment with CPA (30 mumol/l), this contraction was suppressed in SHR and WKY tissues. On the restoration of Ca2+, CPA induced a nifedi pine (5 mumol/l) sensitive contraction, significantly larger in SHR th an in WKY tissues. The relaxation rate to nifedipine of K+-induced con traction in CPA-treated SHR tissue was also reduced. We conclude that the ER Ca2+ pump in SHR aorta is less effective as compared with WKY t issue. The significantly greater CPA-induced contraction together with the reduced relaxation rate in the presence of CPA in SHR tissues as compared with controls suggests that Ca2+ handling was also altered at the plasma membrane.