1
The haemodynamic effects of angiotensin II (AII) and, for comparison, arginine vasopressin (AVP) in the femoral and superior mesenteric artery of urethane‐anaesthetized rats were analysed with the ...ultrasonic transit time shift technique.
2
I.v. bolus injection of AII (0.1–3 nmol kg−1) and AVP (0.03–1 nmol kg−1) increased blood pressure which was accompanied by a decrease in blood flow through the superior mesenteric artery and an increase in femoral blood flow. The femoral hyperaemia was in part due to vasodilatation as indicated by a rise of femoral vascular conductance up to 200% relative to baseline. The femoral vasodilatation caused by AVP, but not AII, was followed by vasoconstriction.
3
Blockade of angiotensin AT1 receptors by telmisartan (0.2–20 μmol kg−1) prevented all haemodynamic responses to AII.
4
The femoral dilator responses to AII and AVP depended on the increase in vascular perfusion pressure since vasodilatation was reversed to vasoconstriction when blood pressure was maintained constant by means of a gravity reservoir. However, the AII‐evoked femoral vasodilatation was not due to an autonomic or neuroendocrine reflex because it was not depressed by hexamethonium (75 μmol kg−1), prazosin (0.25 μmol kg−1) or propranolol (3 μmol kg−1).
5
The AII‐induced femoral vasodilatation was suppressed by blockade of nitric oxide (NO) synthesis with NG‐nitro‐L‐arginine methyl ester (L‐NAME, 40 μmol kg−1) and reversed to vasoconstriction when L‐NAME was combined with indomethacin (30 μmol kg−1), but was left unaltered by antagonism of endothelin ETA/B receptors with bosentan (37 μmol kg−1).
6
These results demonstrate that the effect of AII to increase systemic blood pressure and the resulting rise of perfusion pressure in the femoral artery stimulates the formation of NO and prostaglandins and thereby dilates the femoral arterial bed. This local vasodilator mechanism is sufficient to mask the direct vasoconstrictor response to AII.
British Journal of Pharmacology (1997) 122, 975–984; doi:10.1038/sj.bjp.0701460
Meeting abstracts - A single PDF containing all abstracts in this Supplement is available at http://www.biomedcentral.com/content/files/pdf/1471-2210-10-S1-full.pdf.EMPTY Background Prostaglandin ...(PG) D2 is substantially involved in allergic inflammation and signals via the seven transmembrane (7TM) spanning/G protein-coupled receptors (GPCRs) chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2) and D-type prostanoid (DP) receptor.
... an EP4 antagonist enhanced the PGE2-induced stimulation of platelet aggregation, indicating a potent anti-aggregatory activity of the EP4 receptors. Interestingly, the inhibitory effect of the ...EP4 agonist was brought about by protein kinase C but not adenylyl cyclase, accompanied by attenuated Ca2+ flux, decreased activation of glycoprotein IIb/IIIa and down-regulation of P-selectin.
1
Cholecystokinin octapeptide (CCK‐8) and gastrin‐17 augment gastric mucosal blood flow in the rat. The present study examined whether the gastric vasodilator effect of these peptides is mediated by ...CCKA or CCKB receptors.
2
Intravenous injection of CAM‐1481 (1 mg kg−1), a dipeptoid antagonist of CCKA receptors, or CAM‐1028, a dipeptoid CCKB receptor antagonist (1 mg kg−1), had no effect on basal gastric mucosal blood flow as determined by the clearance of hydrogen in urethane‐anaesthetized rats.
3
Intravenous infusion of CCK‐8 or gastrin‐17 (8–200 pmol min−1) increased gastric mucosal blood flow in a dose‐dependent fashion. The CCKB receptor antagonist, CAM‐1028, significantly attenuated the hyperaemic response to CCK‐8 and gastrin‐17 whereas the CCKA receptor antagonist, CAM‐1481, did not antagonize CCK‐8 but caused a slight attenuation of the vasodilator response to gastrin‐17.
4
The selectivity of the two antagonists was proved by the findings that CAM‐1028, but not CAM‐1481, inhibited gastric acid secretion evoked by CCK‐8 or gastrin‐17 (CCKB receptor assay) while CAM‐1481, but not CAM‐1028, inhibited the CCK‐8‐induced contraction of guinea‐pig isolated gall bladder strips (CCKA receptor assay).
5
These data show that the actions of CCK‐8 and gastrin‐17 to increase mucosal blood flow in the rat stomach are primarily mediated by CCKB receptors.
1
The vasopressin receptor subtype involved in the enhancement by vasopressin of adrenoceptor‐mediated vasoconstriction was investigated in rat isolated perfused mesenteric arteries.
2
...Arg8vasopressin (1–10 nm) dose‐dependently increased the perfusion pressure and enhanced the pressor response to the adrenoceptor agonist methoxamine (40 nmol) or electrical stimulation of periarterial nerves (16 Hz), at the concentration of 10 nm of Arg8vasopressin up to 4 and 3 fold, respectively.
3
During prolonged exposure (45 min) the direct vasoconstrictor effect of Arg8vasopressin (10 nm) rapidly declined whereas the potentiation of methoxamine‐induced vasoconstriction was maintained.
4
The selective vasopressin V1A receptor antagonist SR 49,059 (1–3 nm) and the non‐selective V1A/B and oxytocin receptor antagonist deamino‐Pen1,Tyr(Me)2,Arg8vasopressin (15–45 nm) inhibited the direct vasoconstrictor action of Arg8vasopressin but had no effect on the enhancement of the pressor response to methoxamine or electrical stimulation.
5
The V1B receptor agonist deamino‐Cys1,β‐(3‐pyridyl)‐D‐Ala2,Arg8vasopressin (100–1000 nm) and the V2 receptor agonist deamino‐Cys1,D‐Arg8vasopressin (1–10 nm) were devoid of any pressor activity and did not potentiate methoxamine‐evoked vasoconstriction. In contrast, 1‐triglycyl,Lys8vasopressin (100–1000 nm) potentiated the methoxamine responses without per se inducing vasoconstriction.
6
In arteries precontracted with methoxamine (7.5 μm) pressor responses to Arg8vasopressin (3–10 nm) were not inhibited by a dose of SR 49,059 (3 nm) which abolished the peptide's vasoconstrictor effect under control conditions.
7
These data show that the direct vasoconstrictor effect of Arg8vasopressin is mediated by V1A receptors while the enhancement of adrenoceptor‐mediated pressor responses is insensitive to V1A, V1B, and oxytocin receptor antagonists and is not mimicked by selective agonists of V1B and V2 receptors. In conclusion, an unusual interaction of vasopressin with V1A receptors, or even the existence of a novel receptor subtype, has to be considered.
British Journal of Pharmacology (1998) 125, 1120–1127; doi:10.1038/sj.bjp.0702167
Background & Aims: Gastric acid is known to contribute to ulcer pain, but the mechanisms of gastric chemonociception are poorly understood. This study set out to investigate the pathways and ...mechanisms by which gastric acid challenge is signaled to the brain.
Methods: Neuronal excitation in the rat brainstem and spinal cord after intragastric administration of HCl (0.35–0.7 mol/L) was examined by in situ hybridization autoradiography for the immediate early gene c-fos.
Results: Gastric acid challenge did not induce c-fos transcription in the spinal cord but caused many neurons in the nucleus tractus solitarii and area postrema to express c-fos messenger RNA (mRNA). The HCl concentration–dependent excitation of medullary neurons was in part associated with behavioral manifestations of pain but not directly related to the acid-induced injury and contraction of the stomach. Subdiaphragmatic vagotomy suppressed the c-fos mRNA response to intragastric acid, and morphine inhibited it in a naloxone-reversible manner, whereas pretreatment of rats with capsaicin was without effect.
Conclusions: Gastric acid challenge is signaled to the brainstem, but not the spinal cord, through vagal afferents that are sensitive to acid but resistant to capsaicin. It is hypothesized that the gastric acid–induced c-fos transcription in the brainstem is related to gastric chemonociception.
GASTROENTEROLOGY 1998;115:649-660
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