ABSTRACT
1. The importance of central vasomotor effects of endogenously generated angiotensin in the acute hypertensive response to renal artery constriction has been investigated in the anaesthetized greyhound. 2. When the central cardiovascular action of angiotensin was abolished by thermocoagulation of the areas postrema, the hypertensive response to renal artery constriction was reduced by half while the increase in plasma renin activity was unchanged. 3. It is concluded that central vasomotor effects of angiotensin play a significant role in renin-dependent hypertension.
Subject(s)
Angiotensin II/physiology , Hypertension, Renal/physiopathology , Kidney , Acute Disease , Angiotensin II/pharmacology , Animals , Blood Pressure , Constriction , Dogs , Kidney/drug effects , Kidney/physiology , Norepinephrine/pharmacology , Regional Blood Flow , Renal Artery , Renin/blood , Time FactorsSubject(s)
Aspirin/pharmacology , Hemodynamics/drug effects , Lung/metabolism , Prostaglandins/pharmacology , Animals , Arteries , Biological Assay , Blood Pressure/drug effects , Cardiac Output/drug effects , Central Venous Pressure/drug effects , Depression, Chemical , Dogs , Female , Infusions, Parenteral , Male , Prostaglandins/metabolism , Rats , VeinsSubject(s)
Aspirin/therapeutic use , Shock, Septic/drug therapy , Animals , Biological Assay , Blood Cell Count , Blood Platelets/drug effects , Blood Platelets/metabolism , Blood Pressure/drug effects , Cats , Central Venous Pressure/drug effects , Depression, Chemical , Dogs , Female , Half-Life , Male , Rats , Salicylates/blood , Secretory Rate/drug effects , Serotonin/blood , Serotonin/metabolism , Sheep , Stomach/drug effectsABSTRACT
1. We have examined the central actions of clonidine (2-(2-6-dichlorphenylamine)-2-imidazoline hydrochloride). It has been confirmed that when infused into the vertebral artery at 2 mug/min, it caused a decrease in blood pressure and a slight increase in heart rate. The same dose given intravenously or into the carotid artery had no effect.2. Intravertebral clonidine also greatly reduced the reflex response to carotid occlusion and the effects of an intravertebral infusion of angiotensin (1 ng/kg)/min.3. This central action of clonidine was antagonized by the adrenergic neurone blocking drug bethanidine (4-5 mg/kg intravenously) even after the cervical cord had been transected at C(4)-C(6) suggesting that bethanidine also has central actions.4. Other drugs which also antagonized the central effects of clonidine were guanethidine (4-5 mg/kg intravenously), bretylium (10 mg/kg intravenously) and phentolamine (0.2 mg/kg intravenously).5. It is suggested that there are central adrenergic neurones which inhibit cardiovascular autonomic reflexes and that the central autonomic effects of clonidine are due to stimulation of inhibitory adrenoceptors. The antagonism by adrenergic neurone blocking drugs of the effect of clonidine could therefore be due to blockade of these inhibitory pathways.6. The central action of clonidine could only be demonstrated when a high concentration was infused into the vertebral artery and could not be shown with oral doses of (20 mug/kg)/day for seven days. It is concluded that the hypotensive action of therapeutic doses is unlikely to be due to the central action of clonidine.
Subject(s)
Antihypertensive Agents/pharmacology , Central Nervous System/drug effects , Imidazoles/pharmacology , Angiotensin II/antagonists & inhibitors , Animals , Blood Pressure/drug effects , Bretylium Compounds/pharmacology , Carotid Arteries , Clonidine/administration & dosage , Clonidine/antagonists & inhibitors , Clonidine/pharmacology , Dogs , Guanidines/pharmacology , Heart Rate/drug effects , Injections, Intra-Arterial , Injections, Intravenous , Phentolamine/pharmacology , Receptors, Adrenergic , Reflex/drug effects , Vertebral ArteryABSTRACT
Ablation of the areas postrema in 10 dogs caused a highly significant reduction in the pressor response to intravenous infusions of angiotensin yet was without significant effect on the pressor response to intravenous infusions of noradrenaline. The reduction in the pressor response to angiotensin is almost certainly due to abolition of the specific central autonomic effects of the hormone which are dependent on the integrity of the areas postrema. It is suggested that this central effect also contributes to the cardiovascular response to endogenous angiotensin.
