THE CARDIOVASCULAR RESPONSE TO DIMAPRIT, A SELECTIVE HISTAMINE H₂‐RECEPTOR AGONIST

Abstract

I The cardiovascular responses to dimaprit (S-(3-dimethylaminopropyl) isothiourea), a selective histamine H2-receptor agonist have been studied in anaesthetized cats, dogs, rats and rabbits. 2 Dimaprit lowered systemic arterial blood pressure in all species whether given by intravenous injection or by continuous infusion. Intra-arterial injections or infusions caused vasodilatation in the femoral vascular bed. 3 In the cat, continuous intravenous infusions of dimaprit lowered blood pressure without any significant change in heart rate or cardiac output. The fall in blood pressure was thus due to a decrease in peripheral vascular resistance. 4 Dimaprit, given intravenously, increased coronary and gastric blood flows and there were associated marked reductions in vascular resistance. Small reductions in vascular resistance occurred in skeletal muscle, in the intestine and the kidneys. 5 The histamine H2-receptor antagonists, metiamide and cimetidine, antagonized the depressor and vasodilator responses to dimaprit.

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

“…By the use of the selective histamine H1-receptor antagonist, mepyramine, and the selective histamine H2-receptor antagonist, metiamide, the study (Shimizu and Taira 1980) has also shown that histamine receptors on parasympathetic postganglionic neurons are exclusively of the H1-type but not of the H2-type. Such a conclusion is reinforced by the present results obtained with the histamine H1-receptor agonist, PEA (Durant et al 1975;Owen 1975), and the histamine H2-receptor agonist, dimaprit (Flynn et al 1977;Parsons et al 1977). In the present experiments, like histamine, PEA in the presence of metiamide was capable of producing the early and late salivary responses and the late blood flow response although in producing the responses PEA was far less potent than histamine on a molar basis.…”

“…The present experiments were designed to characterize these histamine receptors on the basis of relative potencies of the selective histamine H1-receptor agonist, 2-(2-pyridyl)ethylamine (PEA) (Durant et al, 1975;Owen 1975) and the selective histamine H2-receptor agonist, dimaprit (Flynn et al 1977;Parsons et al 1977) MATERIALS AND METHODS Experiments were performed on 22 dogs of either sex, weighing 10 to 24 kg. The animals were anesthetized with sodium pentobarbital at a dose of 30 mg/kg i.v.…”

Modification of oestrogen-induced uterine hyperaemia by drugs in the ovariectomized rat

“…The present study has confirmed that histamine may be involved because the antihistamine, mepyramine, in a dose which would normally provide H^receptor antagonism (Szelenyi & Thiemer, 1977), produced over 50 % inhibition of the oestrogeninduced increase in blood flow. Changes in organ blood flow in response to H2 receptor stimulation are variable: blood flow increases in the heart and stomach and decreases in brain, liver, kidneys and adrenal glands (Flynn, Johnston & Owen, 1977). From the results reported here with cimetidine, at a dose level known to produce antagonism of the H2-receptor in the rat (D. Owen, personal communi¬ cation), it would appear that the H2-receptors are not involved in the oestradiol-induced uterine hyperaemia.…”

Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system

“…The development of selective histaminergic agonists, which are assumed to activate selectively H2-receptors (Flynn et al 1977;Owen et al 1979) led us to investigate their myocardial effects in the guinea pig heart and human papillary muscle. The aim of the present study was to characterize the effects of two new H2agonistic compounds, impromidine and dimaprit, on cardiac contractility, myocardial c-AMP levels, and to determine their ability to activate the membrane bound adenylate cyclase activity in a sarcolemmal plasma membrane preparation of guinea pig and human ventricular myocardium.…”