Verapamil inhibits refilling of the sarcoplasmic reticulum (SR) in vascular myocytes- increased blockade in stroke-prone spontaneously hypertensive rats (SHRSP)

Ponni Perumalswami, R. Clinton Webb

Research output: Contribution to journalArticle

Abstract

Based on the capacitive model, emptying of the SR in vascular myocytes secondarily signals calcium (Ca) entry to refill the pool. Thus, increased Ca entry through voltage-operated channels may contribute to the enlarged SR pool of activator Ca observed in vascular myocytes from SHRSP. This study characterizes the sensitivity of this mechanism of Ca entry to verapamil SHRSP and WKY rats. Aortic rings (4mm) from SHRSP and (WKY) rats were placed in organ chambers for measurement of contractile force. Following exposure to phenylephrine (PE) to standardize contractile activity, the strips were made to contract to 10mM caffeine (Caff). The magnitude of contraction to caffeine in Ca-containing solution was greater in SHRSP (96% of PE-induced contraction, n=3) than in WKY segments (60%). The SR pool was then depleted by 2-3 exposures to 10mM Caff in Ca-free buffer, EGTA. Following extinction of the response to caffeine, the arteries were treated with 10μM verapamil to block Ca channels, followed by exposure to an extracellular [Ca] of 3.2 mM. Subsequent to this exposure, the strips were again treated with Caff to induce contraction. This response provides a measure of the relative filling of the SR via the Ca channel. Responses to Caff during the exposure to verapamil were smaller in SHRSP (4%) than inWKY (19%). We conclude that the filling of the SR from an extracellular source is more sensitive to blockade by verapamil in SHRSP than in the WKY. Presumably, this reflects a change in Ca channel function related to SR filling in hypertension.

Original languageEnglish (US)
Pages (from-to)A466
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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