The catecholamines, epinephrine, and norepinephrine bind to B1 receptors and increase cardiac automaticity as well as conduction velocity. B1 receptors also induce renin release, and this leads to an increase in blood pressure. In contrast, binding to B2 receptors causes relaxation of the smooth muscles along with increased metabolic effects such as glycogenolysis.

Beta-blockers vary in their specificity towards different receptors, and accordingly, the effects produced depend on the type of receptor(s) blocked as well as the organ system involved. Some beta-blockers also bind to alpha receptors to some degree, allowing them to induce a different clinical outcome when used in specific settings.

Once beta-blockers bind to the B1 and B2 receptors, they inhibit these effects. Therefore, the chronotropic and inotropic effects on the heart undergo inhibition, and the heart rate slows down as a result. Beta-blockers also decrease blood pressure via several mechanisms, including decreased renin and reduced cardiac output. The negative chronotropic and inotropic effects lead to a decreased oxygen demand; that is how angina improves after beta-blocker usage. These medications also prolong the atrial refractory periods and have a potent antiarrhythmic effect.

Beta-blockers classify as either non-selective and beta-1 selective. There are also beta-2 and beta-3 selective drugs; neither has a known clinical purpose to date. Non-selective agents bind to both beta-1 and beta-2 receptors and induce antagonizing effects via both receptors. Examples include propranolol, carvedilol, sotalol, and labetalol. Beta-1 receptor-selective blockers like atenolol, bisoprolol, metoprolol, and esmolol only bind to the beta-1 receptors; therefore, they are cardio-selective.[2][3][4]

Beta-blockers lower the secretion of melatonin and hence may cause insomnia and sleep changes in some patients.[5]

Alpha-1 receptors induce vasoconstriction and increased cardiac chronotropy; this means agonism at the alpha-1 receptors leads to higher blood pressure and an increased heart rate. In contrast, antagonism at the alpha-1 receptor leads to vasodilation and negative chronotropic, which leads to lower blood pressure and decreases heart rate. Some beta-blockers, such as carvedilol, labetalol, and bucindolol, have additional alpha-1 receptor blockage activity in addition to their non-selective beta receptor blockage. This property is clinically useful because beta-blockers that block the alpha-1 receptor have a more pronounced clinical effect on treating hypertension.[6]

Farzam K, Jan A. Beta Blockers. [Updated 2021 Dec 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532906/

Mechanism of action and side-effects of Beta-Blockers (BBs)

Beta-blockers are now the Fourth-line antihypertensives but are used as first-line drugs in patients with ischemic heart disease, thyrotoxicosis, and a preferred drug in heart failure patients (once on diuretics and ACEI/ARBs).

For the mechanism and the side effects of this group of drugs, please have a look at this table in the link:

https://calgaryguide.ucalgary.ca/beta-blockers-mechanism-of-action-and-side-effects/

Hello Assyfa Atha

Beta-blockers make your heart work less hard. This lowers your heart rate (pulse) and blood pressure.

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-blockers prevent the normal ligand (norepinephrine or epinephrine) from binding to the beta-adrenoceptor by competing for the binding site. This inhibits normal sympathetic effects that act through these receptors. Therefore, beta-blockers are sympatholytic drugs.

Because there is generally some level of sympathetic tone on the heart, beta-blockers are able to reduce sympathetic influences that normally stimulate chronotropy (heart rate), inotropy (contractility), dromotropy (electrical conduction) and lusitropy (relaxation). Therefore, beta-blockers cause decreases in heart rate, contractility, conduction velocity, and relaxation rate.

Vascular smooth muscle has β2-adrenoceptors that are normally activated by norepinephrine released by sympathetic adrenergic nerves or by circulating epinephrine. Compared to their effects in the heart, beta-blockers have relatively little vascular effect because β2-adrenoceptors have only a small modulatory role on basal vascular tone. Nevertheless, blockade of β2-adrenoceptors is associated with a small degree of vasoconstriction in many vascular beds. This occurs because beta-blockers remove a small β2-adrenoceptor vasodilator influence that is normally opposing the more dominant alpha-adrenoceptor mediated vasoconstrictor influence.

Beta blockers suppress plasma angiotensin II levels, a chemical that narrows blood vessels. By doing so, they help widen blood vessels to allow blood to flow more easily, which lowers blood pressure.

Best.

Blood pressure (BP) reflects the combined effects of cardiac output (CO) (arterial blood flow per minute), and the resistance to this flow offered by peripheral vessels. That is, it represents the pressure exerted by the blood against the arterial walls during a cardiac cycle, and can be expressed by the following equation: PA = CO x peripheral vascular resistance (PVR) (McARDLE; KATCH; KATCH, 2003).

The highest and lowest BP values, expressed in millimeters of mercury (mmHg), correspond to systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively (POWERS; HOWLEY, 2000).

According to Wilmore and Costill (2001), SBP represents the highest pressure within the artery and corresponds to cardiac ventricular systole. According to McArdle, Katch and Katch (2003), SBP provides an estimate of the work of the heart and the force that the blood exerts against the arterial walls during systole.

During ventricular relaxation (diastole) the BP decreases, and represents the DBP (POWERS; HOWLEY, 2000). This indicates the peripheral resistance, or the ease with which blood flows from the arterioles into the capillaries, since during diastole, the natural elastic recoil of the arteries provides a continuous pressure, which maintains a constant flow of blood to the periphery, until the next wave of blood (McARDLE; KATCH; KATCH, 2003).

Mean arterial pressure (MAP) represents the average pressure exerted by the blood as it circulates through the arteries. It can be estimated from DBP and SBP as follows: MAP = DBP + [0.333 x (SBP - DBP)] (WILMORE; COSTILL, 2001).

At adequate and reasonably constant levels, BP ensures adequate perfusion of body tissues, whether the individual is at rest or performing different activities, and complex mechanisms interact to maintain pressure within a relatively narrow range of variation (IRIGOYEN et al. , 2003).

Thus, BP levels depend on several physiological factors: CO, blood volume, resistance to flow, and blood viscosity, with an increase in one of these variables increasing BP, while a decrease in one or more variables reduces it ( POWERS; HOWLEY, 2000).

These primary BP determinants are determined by a series of factors (MICHELINI, 1999), with the sympathetic nervous system being responsible for the acute regulation of BP, while the kidneys, above all, regulate the long-term BP (GUYTON; HALL, 1998).

Adrenergic beta-blockers, with regard to effects on cardiovascular system, inhibit chronotropic, inotropic and vasoconstrictor responses to the action of epinephrine catecholamines and norepinephrine on beta-adrenergic receptors1

There are different subtypes of β receptors: β1, β2 and β3. All three are linked to G proteins, which in turn are bound to adenylate cyclase2. The neurotransmitter binding to the receptors causes an increase in the concentration of the second cellular messenger, cyclic adenosine monophosphate (cAMP).

Non-selective beta-blockers: block both β1 adrenergic receptors, found mainly in the myocardium, as the β2 , found in smooth muscle, lungs, blood vessels and other organs1. In consequence, have more pronounced peripheral effects such as increased peripheral arterial resistance and bronchoconstriction.

The most used examples in this category are propranolol, nadolol and timolol. A beta blocker does not selective, pindolol, stands out for presenting activity

intrinsic sympathomimetic, acting as an agonist partial adrenergic and, therefore, presenting less bradycardia and bronchoconstriction than other beta-blockers in this category.

b) Cardioselective: block only β1 receptorsmadrenergic, present mostly in the heart, in the nervous system and kidneys and, therefore, without the undesirable peripheral blocking effects. Nonetheless, in very high doses may also have an effect on β2 receptors.

c) Vasodilating action: manifests itself by antagonism to the peripheral alpha-1 receptor, such as carvedilol and labetalol, and by production of nitric oxide, such as nebivolol.

Rev Bras Hipertens vol.16(4):215-220, 2009. Betabloqueadores adrenérgicos Adrenergic betablockers Luiz Aparecido Bortolotto1 , Fernanda M. Consolim-Colombo

A beta blocker reduces proportionaly the heart rate more than it reduces the cardiac output meaning that the stroke volume increases. The greater stroke volume puts stress on the carotid bodies causing a reflex vasodilation = BP lowering.

There are numerous ways that beta blockers lower blood pressure, including:

1.lowering heart rate: By blocking the actions of epinephrine and norepinephrine, beta blockers inhibit the heart's beta-adrenergic receptors, lowering the heart rate. As a result, the amount and force with which the heart pumps blood decreases, resulting in a reduction in blood pressure.

2.Reduces myocardial contractility: Beta blockers also lessen the force of myocardial contraction, or how hard the heart squeezes. As a result, the heart requires less oxygen and nutrients, which helps relieve angina and avoid heart failure.

3.Reducing the release of renin: Beta blockers lessen the release of renin, an enzyme created by the kidneys that creates angiotensin II.Angiotensin II is an effective vasoconstrictor that can make blood vessels contract, raising blood pressure. Beta blockers aid in dilating blood vessels and lowering blood pressure by reducing renin production.

4.Beta blockers inhibit the sympathetic nervous system, which is in charge of the "fight or flight" reaction that can raise heart rate and blood pressure. This reduces the sympathetic nervous system's activity. In those with diseases like heart failure or a recent heart attack, beta blockers can lower blood pressure and stop heart damage by preventing these effects.