AT(1)-receptor blockade and sympathetic neurotransmission in cardiovascular disease.
1. The present survey is dealing with the interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) in various organs and tissues, with an emphasis on the angiotensin AT-receptors located at the sympathetic nerve endings. 2. Angiotensin II, the main effector of the RAAS is known to stimulate sympathetic nerve traffic and its sequelae in numerous organs and tissues, such as the central nervous system, the adrenal medulla, the sympathetic ganglia and the sympathetic nerve endings. These stimulatory effects are mediated by AT(1)-receptors and counteracted by AT(1)-receptor antagonists. 3. Sympatho-inhibition at the level of the sympathetic nerve ending appears to be a class effect of the AT(1)-receptor blockers, mediated by presynaptic AT(1)-receptors. With respect to the ratio pre-/postsynaptic AT(1)-receptor antagonism important quantitative differences between the various compounds were found. 4. Both the pre- and postjunctional receptors at the sympathetic nerve endings belong to the AT(1)-receptor population. However, the presynaptic receptors belong to the AT(1B)-subtype, whereas the postjunctional receptors probably belong to a different AT(1)-receptor subpopulation. 5. Sympatho-inhibition is a class effect of the AT(1)-receptor antagonists. In conditions in which the SNS plays a pathophysiological role, such as hypertension and congestive heart failure, this property may well be of therapeutic relevance.
Nap
A
A
Departments of Pharmacotherapy, Cardiology and Cardiothoracic Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Balt
J C
JC
Mathy
M J
MJ
Van Zwieten
P A
PA
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1