Neurophysiological responses to angiotensin-(1-7)

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• The brain renin-angiotensin system (RAS) plays a crucial role in regulating cardiovascular function and neuronal activity.
• Angiotensin-(1-7), a heptapeptide product of angiotensin I, is found in brain regions involved in autonomic control.
• The precise actions of angiotensin-(1-7) on central neurons, particularly in the paraventricular nucleus (PVN), remain incompletely understood.

Purpose of the Study:

• To investigate the effects of angiotensin-(1-7) on the spontaneous activity of paraventricular nucleus (PVN) neurons.
• To compare the potency and efficacy of angiotensin-(1-7) with other angiotensin peptides, including angiotensin II and angiotensin III.
• To explore the receptor mechanisms involved in angiotensin-(1-7) action using a selective antagonist and to assess its relationship with vasopressin.

Main Methods:

• Microiontophoresis was used to apply angiotensin-(1-7), angiotensin II, angiotensin III, and vasopressin to PVN neurons in vivo.
• Extracellular neuronal firing activity was recorded to assess the excitatory or inhibitory effects of the applied peptides.
• The effects of the angiotensin receptor subtype 2 (AT2) antagonist CGP 42112A were evaluated on peptide-induced neuronal responses.

Main Results:

• Angiotensin-(1-7) significantly excited most PVN neurons, with a delayed onset and maximal effect compared to angiotensin II and III.
• Angiotensin III demonstrated the highest potency among the tested angiotensin compounds.
• The AT2 antagonist CGP 42112A blocked the excitatory actions of angiotensin II, angiotensin III, and angiotensin-(1-7), and vasopressin showed a weak excitatory effect on PVN neurons.

Conclusions:

• The heptapeptide angiotensin-(1-7) acts as a biologically active neuropeptide in the central nervous system.
• Amino-terminal fragments of angiotensin II, such as angiotensin-(1-7), are not merely inactive degradation products but possess distinct biological activity.
• The findings support the involvement of the angiotensin-(1-7) system in central vasopressinergic pathways and suggest a role for AT2 receptors in mediating these effects.