Calcium sensitivity of isometric force in intact and chemically skinned aortas during the development of aldosterone-salt hypertension in the rat.

McMahon, E G; Paul, R J

doi:10.1161/01.res.56.3.427

Cited by 30 publications

(21 citation statements)

References 21 publications

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“…This finding is consistent with the previous reports showing that neither the pCa-force relationship nor Ca2+-induced myosin phosphorylation were altered in triton-skinned tail arteries from SHRSP (24). It is also consistent with the finding that the pCa-force relationship is not altered in saponin-skinned spastic coronary arteries of miniature pigs, which show hyperresponsiveness to histamine (42) triton skinned aortas from rats with aldosterone-salt hypertension (43).…”

Section: Discussionsupporting

confidence: 93%

Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.

Satoh

Kreutz²,

Wilm³

et al. 1994

J. Clin. Invest.

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The Ca2" responsiveness of vascular smooth muscle myofilaments is not unique: it is increased during neuro-humoral activation and decreased during /3-adrenergic stimulation.In this study we tested whether an augmented Ca2" responsiveness of smooth muscle myofilaments may contribute to the increased coronary tone observed in hypertension using /3-escin-permeabilized coronary arteries from 3-mo-old stroke-prone spontaneously hypertensive rats (SHRSP) and their age matched normotensive reference strain (WKY rats). In intact coronary arteries, the response to 5-hydroxytryptamine (5-HT) but not to KCI was larger in SHRSP than in WKY rats. In (i-escin permeabilized coronary arteries in which the receptor effector coupling is still intact, 5-HT enhanced force at constant submaximal (Ca2") (pCa 6.38) to a greater extent in SHRSP. The Ca2" sensitizing effect of 5-HT was mimicked by GTPyS (0.01-10 IAM); again this effect was larger in SHRSP. In the absence of 5-HT or GTPyS the Ca2" force relation was similar in both groups. Forskolin induced relaxation at constant submaximal (Ca2"). This desensitizing effect was smaller in SHRSP than in WKY rats. In conclusion, this study shows that intracellular signalling pathways involved in modulating the Ca2" responsiveness of coronary smooth muscle myofilaments are altered in the genetically hypertensive animals favoring a hypercontractile state in the coronary circulation. (J. Clin. Invest. 1994Invest. . 94:1397Invest. -1403.) Key words: strokeprone spontaneously hypertensive rat . permeabilized coronary arteries *

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Section: Discussionsupporting

confidence: 93%

Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.

Satoh

Kreutz²,

Wilm³

et al. 1994

J. Clin. Invest.

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“…In fact, the EQo value for calcium in these vessels, 0.38 and 0.37 /xM, respectively, was virtually identical to the value of 0.36 fiM noted in a previous study of sensitivity to calcium in chemically skinned aortas from aldosterone hypertensive and control rats. 19 Similar results have been obtained in studies of skinned vascular preparations from SHR. 20 -21 In conclusion, the results of this study indicate that augmented sensitivity to norepinephrine in mesenteric arteries from DOCA hypertensive rats is not accompanied by a change in agonist affinity or a change in the contractile protein interaction.…”

Section: Casupporting

confidence: 79%

Alpha-adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats.

Storm

Webb

1992

Hypertension

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Increased vascular sensitivity to catecholamines characterizes mineralocorticoid hypertension. The present study investigated three possible sites that may account for this abnormality: agonist affinity, Ca 2+ release from intracellular stores, and Ca 2+ 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% KC1 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 ED 50 for norepinephrine was significantly lower in arteries from DOCA rats (pD 2 , 8.21 ±0.15) than in those from sham controls (pD 2 , 7.24±0.11), agonist affinity, determined by partial blockade with phenoxybenzamine, did not differ between the two groups. In contrast, norepinephrine-stimulated 45 Ca2+ efflux in the absence of extracellular Ca 2+ was significantly greater in arteries from DOCA rats than in those from sham rats. In the presence of ryanodine to deplete intracellular Ca 2+ stores, force development to Ca 2+ was not different in saponin-permeabilized vessels from DOCA rats, indicating that the Ca 2+ 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 Ca 2+ 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 a-adrenergic receptors may be involved. (Hypertension 1992;19:734-738) KEY WORDS • adrenergic receptors • norepinephrine • calcium • vascular smooth muscle • deoxycorticosterone • mineralocorticoid hypertension • sarcoplasmic reticulum I ncreased vascular sensitivity to catecholamines has been well documented in various forms of hypertension and has been implicated in the development of increased peripheral vascular resistance. From a mechanistic standpoint, changes at a number of levels may contribute to observed differences in functional responses of vascular smooth muscle between hypertensive and normotensive control animals: alterations in receptor number or binding properties, 1 changes in postreceptor signal transduction, 2 and cellular changes that may directly affect a functional response, such as differences in the contractile proteins. The present study investigated three possible sites that may account for augmented contractile responsiveness to norepinephrine in mesenteric arteries from mineralocorticoid hypertensive rats. To evaluate agonist affinity, we determined the dissociation constant for norepinephrine using partial, irreversible a-adrenergic blockade with phenoxybenzamine. 3 We assessed agonist-induced mo- Ca2+ efflux. Finally, we examined t...

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“…The higher sensitivity to extracellular Ca 2ϩ in aorta from males is consistent with a lower degree of basal endotheliumdependent relaxation factor (EDRF) production, but could not be attributed to a hyperpolarization factor, under these depolarized conditions. Whether ion channels or myosin isoforms are the dominant factor requires further experimentation, such as with permeabilized fibers (26).…”

Section: Discussionmentioning

confidence: 99%

“…The rings were mounted in a 15-ml organ bath and allowed to equilibrate at 37°C for 1 h in physiological saline solution (PSS), during which the tension was adjusted to 50 mN. This force was chosen because it places the ring at a length within the range for optimal active force generation (26). Our PSS contained (in mM) 118 NaCl, 4.73 KCl, 1.2 MgCl 2, 0.026 EDTA, 1.2 KH2PO4, 2.5 CaCl2, 5.5 glucose and was buffered with 25 NaH2CO3; pH, when bubbled with 95%O2Ϫ5% CO2, was 7.4 at 37°C.…”

Section: Rat Experimental Groupsmentioning

confidence: 99%

Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta

Rutgeerts

Bowman²,

Johnson³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Paul RJ, Bowman PS, Johnson J, Martin AF. Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta. Am J Physiol Regul Integr Comp Physiol 292: R751-R757, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00167.2006.-We reported that estrogen treatment of ovariectomized rats increased uterine smooth muscle contractility and the ratio of the COOH-terminal myosin heavy chain isoform SM1 (204 kDa) and SM2 [200 kDa; Hewett TE, Martin AF, Paul RJ. J Physiol (Lond) 460: 351-364, 1993]. We extended this model to study sex and estrogen effects on vascular contractility. Experimental groups included 10-to 14-wk-old male (M), female (F), ovariectomized female (OF), and OF treated with estrogen (OF&E) for 7 days with a subcutaneous pellet delivery system, resulting in 17␤-estradiol of 85 (OF&E) vs. 5 (OF or M) pg/ml. The SM1-to-SM2 ratio increased from 1.8 to 2.6 in thoracic aorta, similar to uterine muscle. Isometric force was measured in 5-mm segments of intact and endothelium-denuded (Ϫendo) aorta. With KCl, the maximum forces were in the order OF Ϸ M Ͼ OF&E, and ED50 OF&E Ͼ OF Ϸ M. Differences in ED50 with estrogen persisted after endothelial denudation. The decreased force in Ϫendo OF aorta was not seen in OF&E, suggesting that estrogen altered an endothelium-dependent effect. No differences in maximum forces were noted with norepinephrine: ED50 OF Ͼ OF&E Ͼ M. Estrogen treatment, in contrast to KCl, increased sensitivity. Endothelial denudation increased sensitivity but reduced the differences between groups. With ACh relaxation, males were more sensitive than females, and estrogen had no effect. In the abdominal aorta, there were no changes in SM1/SM2 with 17␤-estradiol, and differences in contractility were blunted. In summary, estrogen treatment decreased responses to KCl but increased sensitivity to norepinephrine; male rats always demonstrated the highest contractility. An increase in the COOH-terminal myosin heavy chain isoform SM1-to-SM2 ratio with 17␤-estradiol treatment may underlie the changes observed in contractility.estrogen; vascular sensitivity; isometric force; myosin isoforms; ovariectomy THE OCCURRENCE OF CARDIOVASCULAR diseases is greater in men aged 30 -50 yr compared with women of similar age (15, 16). The incidence of cardiovascular diseases is also greater in postmenopausal compared with premenopausal women, and vascular protective effects of female sex hormones have been proposed (15,16,18,31). Currently, estrogen replacement therapy to postmenopausal women is in widespread use, but its validity is questioned (14,17,23,27,34,36). The mechanism by which sex and/or estrogen may affect the heart is unknown; it is likely to be multifactorial and has been reviewed in detail (30, 40). Estrogen receptors have been identified on both vascular endothelial (4, 10) and smooth muscle cells (5, 21, 22, 29), providing two potential pathways by which estrogen could affect vascular function. In addition, non-receptor-mediated mechanisms may play a role (35). Estroge...

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Calcium sensitivity of isometric force in intact and chemically skinned aortas during the development of aldosterone-salt hypertension in the rat.

Cited by 30 publications

References 21 publications

Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.

Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.

Alpha-adrenergic receptors and 45Ca2+ efflux in arteries from deoxycorticosterone acetate hypertensive rats.

Effects of sex and estrogen on myosin COOH-terminal isoforms and contractility in rat aorta

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