Image for Cardiovascular Pharmacology Concepts, Richard E Klabunde PhD

Cardiovascular Pharmacology Concepts

Richard E. Klabunde, PhD

Clinical Disorders:

Therapeutic Classes:

Mechanism Classes:

Also Visit

Cardiovascular Physiology Concepts 3e textbook cover

Click here for information on Cardiovascular Physiology Concepts, 3rd edition, a textbook published by Wolters Kluwer (2021)


Cardiovascular Physiology Concepts textbook cover

Click here for information on Normal and Abnormal Blood Pressure, a textbook published by Richard E. Klabunde (2013)


Beta-Adrenoceptor Agonists (β-agonists)

General Pharmacology

beta-adrenoceptors Gs protein couplingBeta-adrenoceptor agonists (β-agonists) bind to β-receptors on cardiac and smooth muscle tissues. They also have important actions in other tissues, especially bronchial smooth muscle (relaxation), the liver (stimulate glycogenolysis) and kidneys (stimulate renin release). Beta-adrenoceptors normally bind to norepinephrine released by sympathetic adrenergic nerves, and to circulating epinephrine. Therefore, β-agonists mimic the actions of sympathetic adrenergic stimulation acting through β-adrenoceptors. Overall, the effect of β-agonists is cardiac stimulation (increased heart rate, contractility, conduction velocity, relaxation) and systemic vasodilation. Arterial pressure may increase, but not necessarily because the fall in systemic vascular resistance offsets the increase in cardiac output. Therefore, the effect on arterial pressure depends on the relative influence on cardiac versus vascular β-adrenoceptors. Long-term exposure to β-agonists can cause β-receptor down-regulation, which limits their therapeutic efficacy to short-term application. Beta-agonists, because they are catecholamines, have a low bioavailability and therefore must be given by intravenous infusion.


Beta-agonists bind to beta-adrenoceptors in cardiac nodal tissue, the conducting system, and contracting myocytes.


Cardiac effects

  • Increase contractility
    (+ inotropy)
  • Increase relaxation rate
    (+ lusitropy)
  • Increase heart rate
    (+ chronotropy)
  • Increase conduction velocity
    (+ dromotropy)

Vascular effects

  • Smooth muscle relaxation

Other actions

  • Bronchodilation
  • Hepatic glycogenolysis
  • Pancreatic release of glucagon
  • Renin release by kidneys

The heart has both β1 and β2 adrenoceptors, although the predominant receptor type in number and function is β1. These receptors primarily bind norepinephrine that is released from sympathetic adrenergic nerves. Additionally, they bind norepinephrine and epinephrine that circulate in the blood.

Beta-adrenoceptors are coupled to Gs-proteins, which activate adenylyl cyclase to form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A) that phosphorylates L-type calcium channels, which causes increased calcium entry into the cells. Increased calcium entry during action potentials leads to enhanced release of calcium by the sarcoplasmic reticulum in the heart; these actions increase inotropy (contractility). Gs-protein activation also increases the heart rate by opening ion channels responsible for pacemaker currents in the sinoatrial node. PK-A phosphorylates sites on the sarcoplasmic reticulum, which enhances the release of calcium through the ryanodine receptors (ryanodine-sensitive, calcium-release channels) associated with the sarcoplasmic reticulum. This provides more calcium for binding the troponin-C, which enhances inotropy. Finally, PK-A can phosphorylate myosin light chains, which may also contribute to the positive inotropic effect of beta-adrenoceptor stimulation. In summary, the cardiac effects of a β-agonist are increased heart rate, contractility, conduction velocity, and relaxation rate.

Blood vessels

Vascular smooth muscle has β2-adrenoceptors that have a high binding affinity for circulating epinephrine and a lower affinity to norepinephrine released by sympathetic adrenergic nerves.

Beta-2 vascular relaxationThese receptors, like those in the heart, are coupled to a Gs-protein, which stimulates the formation of cAMP. Although increased cAMP enhances cardiac myocyte contraction (see above), in vascular smooth muscle, an increase in cAMP leads to smooth muscle relaxation. The reason for this is that cAMP inhibits myosin light chain kinase that is responsible for phosphorylating smooth muscle myosin. Therefore, increased intracellular cAMP caused by β2-agonists inhibits myosin light chain kinase, producing less contractile force (i.e., promoting relaxation).

Other tissues

Activation of β2-adrenoceptors in the lungs causes bronchodilation. β2-adrenoceptor activation leads to hepatic glycogenolysis and pancreatic release of glucagon, which increases plasma glucose concentrations. β1-adrenoceptor stimulation in the kidneys causes the release of renin, which stimulates the production of angiotensin II and the subsequent release of aldosterone by the adrenal cortex.

Specific Drugs and Therapeutic Uses

There are several β-agonists that are used clinically to treat heart failure or circulatory shock, all of which are natural catecholamines or analogs. Most β-agonists, however, have some α-agonist activity. One agonist, dopamine, also binds to dopaminergic receptors (D1 receptors) that are found in the systemic vasculature, particularly in the kidneys, and causes vasodilation. These drugs, along with their agonist properties, are given in the table below. 

Drug Receptor Selectivity Clinical Use Comments

β1,  β2

α1,  α2

Anaphylactic shock; cardiogenic shock; cardiac arrest Low concentrations: cardiac stimulation (β1 and β2) and decreased systemic vascular resistance (↓SVR; β2); high concentrations: ↑SVR as Epi binds to α1 and α2, which increases arterial pressure.
Norepinephrine β1,  α1,  α2 Severe hypotension; septic shock Increases SVR: (α1, α2) and arterial pressure; baroreflex-induced bradycardia masks direct stimulatory effects on sinoatrial node. Unlike Epi, Norepi binds weakly to βreceptors.
Dopamine D1 
β1,  α1,  α2
Decompensated heart failure, cardiogenic shock and acute renal failure Precursor of norepinephrine. Low concentrations: ↓SVR (D1); intermediate concentrations: additionally stimulate the heart (β1); high concentrations: stimulate the heart (β1) and ↑SVR as α-receptors bind to the dopamine.
Dobutamine β1 Decompensated heart failure, cardiogenic shock

Primarily β1 selective agonist causing cardiac stimulation with little change in SVR; increases arterial pressure.

Isoproterenol β1,  β2 Bradycardia and atrioventricular block Non-selective β-agonist; net effect is cardiac stimulation (β1) and vasodilation (β2) with little change in pressure.

Side Effects and Contraindications

A major side effect of β-agonists is cardiac arrhythmia. Because these drugs increase myocardial oxygen demand, they can precipitate angina in patients with coronary artery disease. Headache and tremor are also common.

Revised 09/13/22

DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.