What question did this study set out to answer?

To analyze the specific effects of stimulating individual alpha- and beta-adrenoceptor subtypes on action potentials and contractions across different regions of the rabbit heart.

October 1, 1984The Journal of PhysiologyOpen Access

Effects of selective alpha 1‐, alpha 2‐, beta 1‐and beta 2‐adrenoceptor stimulation on potentials and contractions in the rabbit heart.

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Why the study?

What are the effects of selective alpha and beta adrenoceptor stimulation on potentials and contractions in the rabbit heart?

Population

Rabbit heart preparations, including animals pre-treated with 6-hydroxydopamine

Design

Preclinical

Authors

IDIain DukesBiotrend (Portugal)EWE. M. Vaughan WilliamsHaffkine Institute

Discussion

Member takes

Implication

Rabbit heart findings should not change practice; hypothesis-generating for adrenoceptor subtype effects on human repolarization and contractility.

Key Points

To analyze the specific effects of stimulating individual alpha- and beta-adrenoceptor subtypes on action potentials and contractions across different regions of the rabbit heart.
Evaluated isolated rabbit heart preparations (sinus node, Purkinje cells, and papillary muscle) using subtype-selective agonists and antagonists for alpha-1 (St 587, prazosin), alpha-2 (BHT 933, WY 25309), beta-1 (atenolol), and beta-2 (pirbuterol, ICI 118551) receptors.
Tested non-selective agonists (noradrenaline, adrenaline, isoprenaline) combined with selective blockers, as well as phenylephrine and rimiterol.
Assessed preparations from both untreated animals and animals pretreated with 6-hydroxydopamine to chemically eliminate sympathetic nerve responses.
In the sinus node, beta-1 stimulation increased depolarization rate (Vmax), whereas both beta-1 and beta-2 stimulation increased diastolic depolarization slope and accelerated repolarization; alpha-1 stimulation after beta-blockade caused bradycardia via delayed repolarization, while alpha-2 stimulation produced no effect.
In papillary muscle and Purkinje cells, beta-1 stimulation increased peak contractions 3- to 5-fold alongside increased tension development rate, whereas beta-2 stimulation did not augment peak contraction.
Following beta-blockade, alpha-1 stimulation moderately increased peak contractions by up to 47% while prolonging time-to-peak and contraction duration; all response patterns persisted despite sympathetic denervation with 6-hydroxydopamine.

Structured PICO

What are the effects of selective alpha and beta adrenoceptor stimulation on potentials and contractions in the rabbit heart?

Population

Rabbit heart preparations (sinus node, Purkinje cells, papillary muscle), including animals pre-treated with 6-hydroxydopamine

Intervention

Selective alpha 1-, alpha 2-, beta 1-, and beta 2-adrenoceptor agonists and antagonists (including St 587, BHT 933, prazosin, WY 25309, atenolol, ICI 118551, pirbuterol, noradrenaline, adrenaline, isoprenaline, phenylephrine, rimiterol)

Outcome

Electrophysiological potentials (depolarization, repolarization, maximum diastolic potential) and mechanical contractions (peak contractions, rate of tension development, time-to-peak, duration)surrogate

In the rabbit heart, beta 1 and beta 2 adrenoceptor stimulation likely increases inward calcium current, whereas alpha 1 stimulation delays its inactivation.

Cite This Study

Dukes et al. (1984) studied this question.

synapsesocial.com/papers/69d56fb975589c71d767dace https://doi.org/10.1113/jphysiol.1984.sp015436

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Implication

Rabbit heart findings should not change practice; hypothesis-generating for adrenoceptor subtype effects on human repolarization and contractility.

Effects of selective alpha 1‐, alpha 2‐, beta 1‐and beta 2‐adrenoceptor stimulation on potentials and contractions in the rabbit heart.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Effects of selective alpha 1‐, alpha 2‐, beta 1‐and beta 2‐adrenoceptor stimulation on potentials and contractions in the rabbit heart.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider