Vasopressin-induced presynaptic facilitation of sympathetic neurotransmission in the pithed rat.
OBJECTIVE
Several studies have shown that arginine vasopressin (AVP) potentiates the sympathetic nervous transmission in isolated vessels. The present study investigates such a potentiation in the pithed rat model.


METHODS
Male Wistar rats weighing 270-310 g were used. Spinal-cord stimulation was applied, with frequencies of 0.25-4 Hz, in the presence or absence of a subpressor dose of intravenous (i.v.) AVP (1 pmol/kg per min). In addition, the effect of AVP on postsynaptic alpha-adrenoceptor-mediated responses was studied using exogenously administered noradrenaline (NA). For this purpose dose-response curves (DRCs) for NA (i.v.) were constructed.


RESULTS
In the pithed rat model endogenously generated angiotensin II facilitates neurally mediated increments in vascular resistance. Without the administration of the angiotensin II type 1 (AT1) antagonist, irbesartan, the facilitating effect of AVP was not visible. However, after the administration of the AT1 antagonist, irbesartan, the facilitating effect of AVP became apparent. The stimulation-induced rise in diastolic blood pressure (DBP) was enhanced in the presence of AVP from 63.7 +/- 4.5 to 78.6 +/- 4.2 mmHg, at a stimulation frequency of 4 Hz. The vasopressin receptor V1 antagonist, SR-49059, completely inhibited this AVP-induced facilitation, whereas the V2 antagonist, SR-121463B, or the V2 agonist, desmopressin, did not. The DRC of exogenously administered NA was not influenced by AVP.


CONCLUSIONS
The stimulating effect of AVP on sympathetic neurotransmission is completely dependent on the stimulation of presynaptically located V1 receptors. The facilitating effect of angiotensin II on the sympathetic nervous system (SNS) in the pithed rat model masks the facilitating effect of AVP in this preparation.
Streefkerk
Jörn O
JO
Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. J.O.Streefkerk@amc.uva.nl
Mathy
Marie-Jeanne
MJ
Pfaffendorf
Martin
M
van Zwieten
Pieter A
PA
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D000077405:Irbesartan; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000077405:Irbesartan; D009638:Norepinephrine