Histamine Receptors in Peripheral Vascular Beds in the Cat

Abstract

The vasodilator activity of histamine has been studied in anaesthetized cats. Histamine causes dose‐dependent vasodilatation in the vasculature of the hind‐limb and mesentery, perfused with blood at constant flow. Experiments using the selective antagonists mepyramine and metiamide indicate the involvement of both H1‐ and H2‐receptors in the vasodilator responses to histamine. Mepyramine (2.5 × 10−6 mol/kg), causes displacement of the histamine dose‐response curve. This displacement is maximum with a dose‐ratio of about 10. Further dose‐dependent displacement of the dose‐response curve occurred after metiamide (4 × 10−7 mol kg−1 min−1 and 2 × 10−6 mol kg−1 min−1), although these does of metiamide had no effect on histamine responses in the absence of mepyramine. Vasodilator responses could also be elicited by the selective H1‐receptor agonists, 2‐methylhistamine, 2‐(2‐aminoethyl)pyridine and 2‐(2‐aminoethyl)thiazole and the selective H2‐receptor agonist, 4‐methylhistamine. The selectivity of mepyramine and metiamide as histamine receptor antagonists was confirmed by their failure to reduce the vasodilator responses to acetylcholine, isoprenaline and bradykinin.

EVIDENCE FOR BOTH HISTAMINE H1‐ AND H2‐RECEPTORS IN THE GASTRIC VASCULATURE OF THE CAT

“…The nature of the modification of histamine responses by histamine receptor antagonists in the stomach was very similar to the modification previously observed in other peripheral vascular beds by comparable techniques (Flynn & Owen, 1975 displaces the histamine dose-response curve to the right in a variety of vascular beds including cat femoral and superior mesenteric vasculature (Flynn & Owen, 1975 (Flynn & Owen. 1975) and mesenteric vasculature in dogs (Pawlik et al, 1977), where there is no evidence that H2-receptor vasodilatation would function via metabolic needs suggest the presence of H2-receptors on gastric blood vessels.…”

“…Two (Flynn & Owen, 1975 Durant, Ganellin & Parsons, 1975) and dimaprit (an H2-receptor agonist, Parsons, Owen, Durant & Ganellin, 1977 …”

Characterization of neuronal and vascular histamine receptors mediating the salivary and vasodilator responses to histamine of the dog submandibular gland.

“…In the present experiments the dose-response curves for the early blood flow responses to PEA and histamine in the presence of metiamide were parallel, and in producing the early blood flow response, PEA was about 40 times less potent than histamine on a molar basis. The value is roughly equal to that obtained in the hind-limb vascular bed of the cat (Flynn and Owen 1975) and that obtained for the vasodepressor effect (Hunt and Fosbinder 1942). In the presence of mepyramine the dose-response curves for the early blood flow response to dimaprit and histamine were also parallel, but dimaprit was about 750 times less potent than histamine in producing the early blood flow response on a molar basis.…”

A COMPARISON OF THE EFFECTS OF BRADYKININ, 5‐HYDROXYTRYPTAMINE AND HISTAMINE ON THE HEPATIC ARTERIAL AND PORTAL VENOUS VASCULAR BEDS OF THE DOG: HISTAMINE H1 AND H2‐RECEPTOR POPULATIONS

“…histamine although if given after mepyramine it causes a further antagonism of these responses (Black et al, 1975). A similar pattern of antagonism to the vasodilator effects of histamine has been reported in the femoral and superior mesenteric arterial vascular beds of the cat (Flynn & Owen, 1975).…”