9-10-dihydroergosine and ergosine

The effect of acute and chronic administration of two ergot derivatives, dihydroergosine (DHESN) and ergosinine (ESNN), on blood pressure, heart rate, cardiac output and total peripheral resistance was studied in conscious spontaneously hypertensive rats. Acute administration of either DHESN or ESNN (50-100 micrograms/kg) resulted in prompt and significant (p less than 0.01) decrease of both blood pressure and heart rate, which lasted for more than 12 h. The decrease in blood pressure was due to reduction in total peripheral resistance, as cardiac output remained unchanged. Prolonged treatment (50 micrograms/kg, i.p., every second day for 12 days) with either DHESN or ESNN significantly (p less than 0.01) decreased blood pressure. In chronically treated rats, total peripheral resistance was found to be decreased while no changes in cardiac output and heart rate were observed. The results indicate that both DHESN and ESNN are potent antihypertensive agents, due to their vasodilator effects. The hypotensive effect of DHESN could be partially blocked by haloperidol, but not by yohimbine. Both, DHESN and ESNN antagonized the effect of phenylephrine on blood pressure.

Topics: Animals; Blood Pressure; Cardiac Output; Ergotamines; Female; Heart Rate; Hemodynamics; Hypertension; Male; Rats; Rats, Inbred SHR; Time Factors; Vascular Resistance

The effects of ergosinine (ESNN), dihydroergosine (DHESN) and dihydroergotamine (DHE) on contractions of the isolated terminal and middle segments of the guinea-pig ileum were studied in-vitro. Responses to cholinergic (3 Hz) and adrenergic stimulation (30 Hz in the presence of atropine) were inhibited, albeit at high concentrations of all three alkaloids (1-30 micrograms ml-1). Cholinergic neurotransmission was surprisingly more affected than adrenergic transmission. Noradrenaline (NA) contractions, however, were inhibited at very low concentrations (1-30 ng ml-1) with the following order of potency: DHESN = DHE greater than ESNN. Prazosin was equally as potent as DHESN in inhibiting NA contractions and similarly potent in inhibiting responses to adrenergic stimulation. ESNN, DHESN and DHE when used at concentrations from 1-30 micrograms ml-1 were also found to inhibit 5-hydroxytryptamine greater than histamine greater than acetylcholine greater than KCl contractions. The results suggest that the principal pharmacological action of ESNN, DHESN and DHE on the guinea-pig isolated ileum is the antagonism to NA on the postsynaptic and extrajunctional population of alpha-adrenoceptors. The neurotransmission, adrenergic as well as cholinergic, appeared to be inhibited via a non-specific presynaptic mechanism presumably regulating the transmitter release. Anti-5-hydroxytryptamine, anti-acetylcholine and antihistamine actions were obtained at similar and relatively high concentrations, thus pointing to a non-specific depressant action upon a common mechanism regulating the contractility of the smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetylcholine; Animals; Dihydroergotamine; Ergotamines; Guinea Pigs; Ileum; In Vitro Techniques; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Norepinephrine; Parasympathetic Nervous System; Synaptic Transmission