Archives
The rank order of agonist potency in turkey cardiac
The rank order of agonist potency in turkey cardiac chambers demonstrated the predominant presence of the β-adrenergic receptor subtype, in line with the receptor classification by . However, a previous radioligand binding study in the left ventricles of 7-week old turkeys reported the existence of both β- and β-subtypes at a ratio of 3:1 (). There are several explanations for this discrepancy. In contrast to our study, binding studies by were carried out at 30 °C in the presence of the lipophilic β-adrenergic receptor antagonist propranolol. Furthermore, to determine β-adrenergic receptors, higher ICYP concentrations and less purified membrane preparations were used possibly impeding the exclusion of large amounts of nonspecific ICYP binding.
The β-adrenergic receptor density in the cardiac chambers of 16-week old turkeys was two times lower than the B obtained in the left ventricle of 7-week old turkeys, presumably for the reasons described above and the different ages of the Cephalexin (). To the best of our knowledge, there are no peer-reviewed studies available that describe the distribution and properties of β-adrenergic receptors in the four cardiac chambers of other avian species. The observation that the β-adrenergic receptor subtype is predominantly present in all cardiac chambers of turkeys suggests that heart dysfunction and treatments may be related to this receptor subtype, although this remains to be elucidated.
Conflict of interest statement
Acknowledgements
We thank the German Federal Ministry for Economic Affairs and Energy for Financial Support of the project (16NK016226). We are also grateful to Ina Hochheim for technical assistance.
The antihypertensive (HTN) effect of beta-adrenergic receptor blockers (β-blockers) was first documented by Pritchard and Gillam over a half century ago., Propranolol was the first β-blocker approved as an oral antiHTN agent. Propranolol was also used as an adjunct therapy to phentolamine, an α-adrenergic blocker, in the treatment of pheochromocytoma., Ultimately, labetalol, a combined α-β-blocker, in its intravenous form, was demonstrated to be of clinical use in the treatment of HTN emergencies and in an oral form for HTN urgencies.,
To date, 14 β-blockers have received Federal Drug Administration approval for oral use in patients having systemic hypertension (HTN; ). Sustained-release formulations of metoprolol, propranolol, and carvedilol have allowed these short-acting β-blockers to be used once daily in HTN.
Mechanism of action
There is no consensus as to the exact mechanism(s) by which β-blockers lower blood pressure (BP), and it is likely that multiple modes of action are involved (Table 2).
Clinical experiences
Heterogeneity among β-blockers
β-Blockers as a group have similar therapeutic effects, despite their structural differences. Their varied aromatic ring structures (Fig 1) confer many pharmacokinetic differences, including completeness of gastrointestinal absorption, degree of first-pass hepatic metabolism, lipid solubility, protein binding, volume of distribution, penetration into the central nervous system, concentration in the myocardium, rate of hepatic biotransformation, pharmacologic activity of metabolites, and renal clearance. The relevance of these variations depends on the clinical conditions present in the individual being treated. In contrast to other classes of antiHTN drugs, important differences in intrinsic chemical properties of β-blockers (Table 1) can translate into significant differences in their clinical effects.
Other applications
The therapeutic efficacy and safety of β-blockers have been well established after 50 years of clinical experience. Their clinical utility has been well documented in patients with angina pectoris, cardiac arrhythmias, aortic dissection, congestive cardiomyopathy, and for reducing the risk of mortality and possibly nonfatal reinfarction in survivors of acute MI.27., 28. Of course, not all of the agents in the class of β-blockers have shown benefit in each of the clinical applications listed above. Most anti-HTN drugs, including β-blockers, can reduce LV mass and wall thickness, although β-blockers have been found to be less effective in this regard than diuretics, angiotensin converting enzyme inhibitors (ACEIs), CCBs and angiotensin receptor blockers (ARBs).4., 29. β-Blockers may be useful as a primary protection against CV morbidity and mortality in certain HTN patients. The drugs have also been found to be of use for a host of other CV and non-CV disorders.3., 30.