Conscious Renal Hypertensive Rats Research Articles

Synthetic phosphatidylethanolamines as renin inhibitors.

SummaryAnti-renin and hypotensive effects of synthetic PEs were examined.(i) Eighteen PEs including optical isomers were newly synthesized. Arachidonic acid, linolenic acid, and stearic acid were substituted at the positions of β, γ, or both. Natural PE was extracted from porcine kidney, and the lyso form was prepared by treatment of phospholipase A.(ii) Anti-renin activity of these compounds was determined using high-renin plasma obtained from the dog. The inhibition of renin activity was expressed as a percentage of the reduction in the production rate of angiotensin I as measured by radioimmunoassay.(iii) The inhibitory effects of PE(β-C18=3, γ-C18) series, d- and DL-PE(β-C20=4, γ-C18), and dl- and l-PE(β-C18, γ-C20=4) were greater than that of the natural PE, but did not exceed the effect of lyso-PE.(iv) Hypotensive effect was evaluated in conscious normotensive, spontaneously hypertensive, and renal hypertensive rats by daily im injection of the test compounds.(v) Following repeated administration of...

Evidence for the involvement of α-adrenoceptor blockade in the antihypertensive action of diazoxide in the renal hypertensive rat

The effects of diazoxide on the blood pressure and heart rate of conscious renal hypertensive rats have been investigated. The antihypertensive action of diazoxide has been studied in relation to the effects of diazoxide pretreatment on pressor responses to stimulation of the complete sympathetic outflow and to injections of noradrenaline, phenylephrine, angiotensin and serotonin in pithed rats. In pithed preparations, pressor responses to sympathetic nerve stimulation, and to injected noradrenaline and phenylephrine were significantly reduced by diazoxide pretreatment, at a time corresponding to maximal reduction of blood pressure in conscious animals. At this time there was no significant reduction of pressor responses to injected angiotensin or serotonin. These findings suggest a contribution of α-adrenoceptor blockade to the antihypertensive activity of diazoxide.

Central inhibitory effect of alpha-methyldopa on blood pressure, heart rate and body temperature of renal hypertensive rats.

The central inhibitory effect of alpha-methyldopa on blood pressure, heart rate and body temperature was studied in conscious renal hypertensive rats. Systemic administration of alpha-methyldopa decreased mean arterial blood pressure and body temperature and caused a short lasting increase in heart rate followed by a long lasting decrease. Inhibition of central decarboxylase activity prevented the decrease in blood pressure, heart rate and body temperature but not the initial increase in heart rate. Inhibition of peripheral decarboxylase activity blocked the increase in heart rate and partially reduced the decrease in heart rate and body temperature but did not affect the decrease in blood pressure. Alpha-Methyldopa also decreased blood pressure at an ambient temperature of 30 degrees C, but the decrease of body temperature was absent and the heart rate remained elevated for 7 hr. Similar results were obtained in normotensive rats. The decrease in heart rate was correlated with the decrease in body temperature in normotensive and renal hypertensive rats. These findings suggest that in the renal hypertensive rat the decrease in blood pressure and in body temperature depends on a central action of alpha-methyldopa metabolites.