The Effects of Ca<sup>2+</sup> Antagonists on Isolated Rat and Rabbit Mesenteric Resistance Vessels<sup>a</sup>

Cauvin, C.; Tejerina, M.T.; Hwang, Ok Jin; Kai-Yamamoto, M.; Breemen, Cornelis van

doi:10.1111/j.1749-6632.1988.tb33375.x

Cited by 19 publications

(5 citation statements)

References 19 publications

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“…Finally, in addition to agonist effect at the cell membrane, contractile agonist sensitivity to calcium channel antagonists depends also on the extent to which that agonist mobilizes intracellular calcium (22). An expected finding was the reduced overall effectiveness of calcium channel antagonists during NEinduced contraction, which depends in part on intracellular Ca2+, compared to KC1-induced tone at all ages.…”

Section: Discussionmentioning

confidence: 99%

Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

et al. 1991

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ABSTRACT. We examined the ontogeny of relaxation function may vary depending on the site of binding within responses to three categories of calcium channel antagothe calcium channel. (Pediatr Res 29: 278-281, 1991) nists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCI-mediated) and receptorAbbreviations operated channels [norepinephrine (NE)-mediated] in rat thoracic aorta. Aortic rings from 2-to 3-d, 1-wk, and 12-wk-old Sprague Dawley rats were mounted in an organ bath, bathed in Krebs' solution, and connected to a forcedisplacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single EDso of isotonic KC1 or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 pM verapamil, 1 pM diltiazem, or 0.1 pM nifedipine, followed by another dose of KC1 or NE.Verapamil and diltiazem demonstrated significant (p c 0.05) age-related increases in effectiveness for blocking KCI-mediated contraction [(% reduction of control contraction f SEM) (Verapamil: 2-3 d, 67.7 f 4.2; 1 wk, 72.5 f 1.8; 12 wk, 89.5 f 1.0. Diltiazem: 2-3 d, 64.6 f 2.9; 1 wk, 73.5 f 3.0; 12 wk, 83.1 f: 1.81. Nifedipine was equally effective at all ages: 2-3 d, 85.6 f 1.3; 1 wk, 90.0 f 1.6; and 12 wk, 91.3 f 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2-3 d, 6.2 f 3.9; 1 wk, 28.0 f 4.8; 12 wk, 44.1 f 6.0. Diltiazem: 2-3 d, 8.0 f 3.1; 1 wk, 20.5 f 3.9; 12 wk, 46.5 f 4.8). Again, nifedipine was equally effective at all ages: 2-3 d, 42.0 f 6.8; 1 wk, 35.8 f 3.9; and 12 wk, 37.5 f 3.2. In summary, for the categories of calcium channel antagonists that interact at the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) binding sites, there were age-related increases in effectiveness for blocking both potentialoperated and receptor-operated channels. However, for nifedipine, which binds to the 1,4-dihydropyridine binding site, no maturational change was observed. These results suggest that the ontogeny of calcium channel antagonists' We have previously (8) demonstrated the ontogeny of the concentration-dependent response in thoracic aortic rings among 2-d-, 1-wk-, and 1 Zwk-old rats for both potential-mediated (KClinduced) and receptor-mediated (NE-induced) contraction. Thus, calcium channel function is present from 2 d of age with perhaps increasing physiologic function during development. However, many aspects of calcium channel function during ontogeny are unknown. We therefore designed the present study to examine one aspect of calcium channel function, viz. the ontogeny of responses to three categories of calcium channel antagonists for KCI-and NE-mediated contraction in rat aorta. The objectives were 3-fold: to determine if there were 1) agerelated differences in response to selective calcium channel antagonists; 2) differential effects among the three categories of calcium channel antagonists; and 3 ) differe...

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Section: Discussionmentioning

confidence: 99%

Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

et al. 1991

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“…With few exceptions, vasoconstrictor agonists that act through G q/11 -coupled receptors cause contraction of SMCs in blood vessels that can be inhibited, at least in part, by organic L-type VGCC blockers (53, 55, 133, 138, 146, 211, 212, 369, 482, 532, 611, 635, 657, 808, 809, 901, 959, 1007, 1073, 1075, 1138, 1242, 1337, 1367, 1447, 1449, 1545, 1649). This is due to not only agonist-induced depolarization of the SMC membrane, but also to a direct augmentation of the function of L-type VGCCs by the agonists (611).…”

Section: Voltage-gated Ca2+ Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

269

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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“…Calcium channel blockers are thought to inhibit voltage-dependent Ca 2+ channels and these are not activated by norepinephrine (Cauvin and Van Breeman, 1987;Godfrind, 1988;Kamp and Miller, 1987;Van Zwieten and Timmermans, 1988). However, it has been shown recently that, at least in some experimental systems, Ca 2÷ channel blockers can also inhibit receptor-dependent Ca 2+ channels, particularly after ~2-agonist stimulation (Cauvin et aL, 1988). Thus, the inefficiency of Ca 2+ channel blockers suggests that receptor~lependent Ca 2+ channels are not involved in the norepinephrine-induced vasoconstriction of the hepatic microcirculation and that other mechanisms may occur, e.g.…”

Section: ) Phenylephrinementioning

confidence: 99%

Hepatic circulation: Potential for therapeutic intervention

Ballet

1990

Pharmacology & Therapeutics

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In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions.

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The Effects of Ca²⁺ Antagonists on Isolated Rat and Rabbit Mesenteric Resistance Vessels^a

Cited by 19 publications

References 19 publications

Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Hepatic circulation: Potential for therapeutic intervention

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The Effects of Ca2+ Antagonists on Isolated Rat and Rabbit Mesenteric Resistance Vesselsa

Cited by 19 publications

References 19 publications

Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Hepatic circulation: Potential for therapeutic intervention

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The Effects of Ca²⁺ Antagonists on Isolated Rat and Rabbit Mesenteric Resistance Vessels^a