α-Adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats

Deborah S. Storm, R. Clinton Webb

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Increased vascular sensitivity to catecholamines characterizes mineralocorticoid hypertension. The present study investigated three possible sites that may account for this abnormality: Agonist affinity, Ca2+ release from intracellular stores, and Ca2+ sensitivity of the contractile proteins. Adult male Sprague-Dawley rats underwent uninephrectomy and were implanted subcutaneously with deoxycorticosterone acetate (DOCA; 200 mg/kg, 1% NaC10.2% KCl drinking water, 4–6 weeks). Control rats were sham treated. Helical strips of mesenteric arteries were placed in muscle baths for measurement of isometric force development. Although the ED50 for norepinephrine was significantly lower in arteries from DOCA rats (pD2, 8.21±0.15) than in those from sham controls (pD2, 7.24±0.11), agonist affinity, determined by partial blockade with phenoxybenzamine, did not differ between the two groups. In contrast, norepinephrine-stimulated 45Ca2+ efflux in the absence of extracellular Ca2+ was significantly greater in arteries from DOCA rats than in those from sham rats. In the presence of ryanodine to deplete intracellular Ca2+ stores, force development to Ca2+ was not different in saponin-permeabilized vessels from DOCA rats, indicating that the Ca2+ sensitivity of the contractile proteins was not altered in DOCA hypertension. We conclude that increased vascular sensitivity to norepinephrine in mineralocorticoid hypertension is related to increased release of Ca2+ from a subcellular store and not to changes in agonist affinity or to the contractile protein interaction. Based on previous reports, it is likely that this abnormality reflects a postreceptor change in signal transduction, but there is also evidence to suggest that an increase in the number of α-adrenergic receptors may be involved.

Original languageEnglish (US)
Pages (from-to)734-738
Number of pages5
JournalHypertension
Volume19
Issue number6
StatePublished - Jun 1992
Externally publishedYes

Fingerprint

Desoxycorticosterone Acetate
Desoxycorticosterone
Adrenergic Receptors
Acetates
Arteries
Contractile Proteins
Mineralocorticoids
Norepinephrine
Hypertension
Blood Vessels
Phenoxybenzamine
Ryanodine
Mesenteric Arteries
Saponins
Baths
Drinking Water
Catecholamines
Sprague Dawley Rats
Signal Transduction
Muscles

Keywords

  • Adrenergic receptors
  • Calcium
  • Cascular smooth muscle
  • Deoxycorticosterone
  • Mineralocorticoid hypertension
  • Norepinephrine
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Internal Medicine

Cite this

α-Adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats. / Storm, Deborah S.; Webb, R. Clinton.

In: Hypertension, Vol. 19, No. 6, 06.1992, p. 734-738.

Research output: Contribution to journalArticle

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abstract = "Increased vascular sensitivity to catecholamines characterizes mineralocorticoid hypertension. The present study investigated three possible sites that may account for this abnormality: Agonist affinity, Ca2+ release from intracellular stores, and Ca2+ sensitivity of the contractile proteins. Adult male Sprague-Dawley rats underwent uninephrectomy and were implanted subcutaneously with deoxycorticosterone acetate (DOCA; 200 mg/kg, 1{\%} NaC10.2{\%} KCl drinking water, 4–6 weeks). Control rats were sham treated. Helical strips of mesenteric arteries were placed in muscle baths for measurement of isometric force development. Although the ED50 for norepinephrine was significantly lower in arteries from DOCA rats (pD2, 8.21±0.15) than in those from sham controls (pD2, 7.24±0.11), agonist affinity, determined by partial blockade with phenoxybenzamine, did not differ between the two groups. In contrast, norepinephrine-stimulated 45Ca2+ efflux in the absence of extracellular Ca2+ was significantly greater in arteries from DOCA rats than in those from sham rats. In the presence of ryanodine to deplete intracellular Ca2+ stores, force development to Ca2+ was not different in saponin-permeabilized vessels from DOCA rats, indicating that the Ca2+ sensitivity of the contractile proteins was not altered in DOCA hypertension. We conclude that increased vascular sensitivity to norepinephrine in mineralocorticoid hypertension is related to increased release of Ca2+ from a subcellular store and not to changes in agonist affinity or to the contractile protein interaction. Based on previous reports, it is likely that this abnormality reflects a postreceptor change in signal transduction, but there is also evidence to suggest that an increase in the number of α-adrenergic receptors may be involved.",
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