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)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

sarcoplasmic reticulum
verapamil
Sarcoplasmic Reticulum
Inbred SHR Rats
Verapamil
stroke
blood vessels
myocytes
Muscle Cells
Blood Vessels
caffeine
Caffeine
Rats
Stroke
Calcium
calcium
rats
calcium channels
Calcium Channels
phenylephrine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

@article{d14df05c90a24aa0a564207bffd0462a,
title = "Verapamil inhibits refilling of the sarcoplasmic reticulum (SR) in vascular myocytes- increased blockade in stroke-prone spontaneously hypertensive rats (SHRSP)",
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.",
author = "Ponni Perumalswami and Webb, {R Clinton}",
year = "1997",
month = "12",
day = "1",
language = "English (US)",
volume = "11",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Verapamil inhibits refilling of the sarcoplasmic reticulum (SR) in vascular myocytes- increased blockade in stroke-prone spontaneously hypertensive rats (SHRSP)

AU - Perumalswami, Ponni

AU - Webb, R Clinton

PY - 1997/12/1

Y1 - 1997/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33750268568&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750268568&partnerID=8YFLogxK

M3 - Article

VL - 11

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -