Role of Prostaglandins on the Renin-Angiotensin System in Normotensive and Hypertensive Rats

ABSTRACT

BACKGROUND: Prostaglandin system is known to participate in manifestation of the renin-angiotensin system. However, role of prostaglandins on the renin-angiotensin system in development of hypertension is not well established. This study was to examine whether the role of prostaglandins is altered in experimental hypertension. METHODS: Two-kidney, one-clip(2KIC) renal hypertension was made by clipping the left renal artery with a silver clip(internal gap of 0.2mm) and deoxycorticosterone acetate (DOCA)-salt hypertension by subcutaneous implantation of DOCA(200mg/kg) strip plus saline(1%) drinking. They were used 3 weeks later. Age-matched normal rats served as a control. Femoral artery was cannulated and arterial blood pressure and heart rate were monitored continuously. RESULTS: 1) In normotensive rats, saralasin infusion(20 microg/kg/min, IV) caused a decrease in mean arterial pressure without significant alterations in heart rate. Indomethacin-pretreatment(10mg/kg, IP) abolished the depressor response to saralasin. 2) The depressor response to saralasin was more marked in renal hypertensive rats than in normotensive rats. The magnitude of maximum decrease in blood pressure, however, was comparable between the hypertensive and normotensive rats. Indomethacin-pretreatment did not affect the depressor response to saralasin in renal hypertensive rats. 3) In DOCA-salt hypertensive rats, saralasin infusion rather caused an increase in mean arterial pressure without significant alterations in heart rate. The pressor response to saralasin was not affected by indomethacin-pretreatment. CONCLUSION: These results indicate that prostaglandin system may modify renin-angiotensin system in normotensive rats. It is suggested that mechanisms other than prostaglandin system participate in the full-blown manifestation of renin-angiotensin system in 2KIC renal hypertensive rats.