Central blood pressure effects of substance P and angiotensin II: Role of the sympathetic nervous system and vasopressin

doi:10.1016/0014-2999(81)90384-8

European Journal of Pharmacology

Volume 71, Issue 1, 24 April 1981, Pages 33-42

https://doi.org/10.1016/0014-2999(81)90384-8 Get rights and content

Abstract

The role of the sympathetic nervous systme and of arginine vasopressine (AVP) in the mediation of the central cardiovascular effects of angitotensin II (ANG II) and substance P (SP) was investigated. ANG II and SP caused dose-dependent blood pressure increases when injected into the lateral brain ventricle (i.c.v.) of conscious rats; ANG II was tenfold more potent than SP. Peripheral blockade of α-adrenoceptors with prazosin or blockade of the vasopressor action of AVP by the AVP antagonist d(CH₂)₅ VDAVP both partially inhibited the pressor responses to central ANG II. Combined treatment with the two blockers produced almost complete inhibition of the central ANG II responses. Substance P injected i.c.v. produced increases in noradrenaline and adrenaline but not AVP in the plasma. Peripheral α-receptor blockade by prazosin reversed the central pressor effects of SP to depressor responses. The AVP antagonist did not alter the cardiovascular responses to SP. It is concluded that in onscious animals, stimulation of the sympathetic nervous system and release of AVP contribute to the central pressor action of ANG II to a similar extent and independently of each other. In contrast, the central pressor responses to SP appear to be exclusively mediated by the sympathetic nervous system without participation of AVP.

References (33)

M. Da Prada et al.
Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within femtomol range
Life Sci.
(1976)
R.A. Gillis et al.
Evidence that substance P is a neurotransmitter of baro- and chemoreceptor afferents in nucleus tractus solitarii
Brain Res.
(1980)
W.E. Hoffman et al.
Independent receptors for pressor and drinking responses to central injections of angiotensin II and carbachol
Brain Res.
(1977)
I.A. Reid et al.
Interactions and properties of some components of the renin-angiotensin system in rat brain
W.Z. Traczyk et al.
The pressor response to substance P and hexapeptide [pGlu⁶]-SP_6–11 injections into the cerebral ventricles in rats
Neuropharmacology
(1980)
L.F. Agnati et al.
Evidence for a possible role of substance P and/ or its fragments in the central cardiovascular regulation
Neurosci. Lett. Suppl.
(1979)
M. Bellet et al.
Central cardiovascular effects of narcotic analgesics and enkephalins in rats
Br. J. Pharmacol.
(1980)
B. Delbarre et al.
Possible interaction between analgesia and central blood pressure regulation: role of opioids and naloxone
IRCS Med. Sci.
(1980)
W. Feldberg et al.
Central cardiovascular effects of enkephalins and C-fragment of lipotropin
J. Physiol. (London)
(1978)
D. Ganten et al.
Central peptidergic stimulation: its possible contribution to blood pressure regulation

A.R. Granata et al.

A central hypertensive action of substance P in rats

IRCS Med. Sci.

(1980)

D. Haack et al.

Vasopressin-mediated blood pressure response to intraventricular injection of angiotensin II in the rat

Pflüger's Arch.

(1978)

G. Haeusler et al.

Evidence for a transmitter function of substance P at the first synapse of the baroreceptor reflex

Naunyn-Schmiedeb. Arch. Pharmacol.

(1980)

K.G. Hofbauer

Effect of a competitive antagonist of arginine vasopressin (AVP) in glycerol-induced acute renal failure (ARF) in rats

Naunyn-Schmiedeb. Arch. Pharmacol.

(1980)

T. Hökfelt et al.

Aminergic and peptidergic pathways in the nervous system with special reference to the hypothalamus

H.W. Hunter et al.

Preparation of iodine-131 labelled human growth hormone of high specific activity

Nature

(1962)

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Central blood pressure effects of substance P and angiotensin II: Role of the sympathetic nervous system and vasopressin

Abstract

Life Sci.

Brain Res.

Brain Res.

Neuropharmacology

Evidence for a possible role of substance P and/ or its fragments in the central cardiovascular regulation

Neurosci. Lett. Suppl.

Central cardiovascular effects of narcotic analgesics and enkephalins in rats

Br. J. Pharmacol.

Possible interaction between analgesia and central blood pressure regulation: role of opioids and naloxone

IRCS Med. Sci.

Central cardiovascular effects of enkephalins and C-fragment of lipotropin

J. Physiol. (London)

Central peptidergic stimulation: its possible contribution to blood pressure regulation

A central hypertensive action of substance P in rats

IRCS Med. Sci.

Vasopressin-mediated blood pressure response to intraventricular injection of angiotensin II in the rat

Pflüger's Arch.

Evidence for a transmitter function of substance P at the first synapse of the baroreceptor reflex

Naunyn-Schmiedeb. Arch. Pharmacol.

Effect of a competitive antagonist of arginine vasopressin (AVP) in glycerol-induced acute renal failure (ARF) in rats

Naunyn-Schmiedeb. Arch. Pharmacol.

Aminergic and peptidergic pathways in the nervous system with special reference to the hypothalamus

Preparation of iodine-131 labelled human growth hormone of high specific activity

Nature