Influence of prostaglandin inhibition on dihydralazine induced acute effects in patients with essential hypertension.
In order to determine whether vasodilator prostaglandins (PG) contribute to the acute vascular and endocrine responses to intravenously administered dihydralazine, we examined its effects on systolic and diastolic blood pressure (BP), heart rate (HR), plasma renin activity (PRA) and the plasma catecholamines (CA) noradrenaline (NA), adrenaline (A) and dopamine (DA) as well as on sodium, potassium and creatinine clearance (CNa, CK and CCr respectively), urinary flow rate, urinary catecholamines (NA, A, DA) and iPGE2 and i6-keto-PGF1 alpha excretion rate in six patients (three females, three males) with essential hypertension before and after PG synthesis inhibition by the nonsteroidal, anti-inflammatory agent diclofenac. Diclofenac, which reduced urinary iPGE2 and i6-keto-PGF1 alpha excretion by 62% (P = 0.026) and 45% (P = 0.037), respectively, antagonized dihydralazine induced diastolic BP reduction (P = 0.0009), HR increase (P = 0.01), noradrenaline and adrenaline increase in plasma (P = 0.02 and P = 0.05, respectively), increase in urine flow rate (P = 0.03), sodium clearance (P = 0.01) and tended to reduce PRA. We conclude that dihydralazine-mediated changes can be reduced by cyclo-oxygenase inhibition, most likely on the basis of a reduction of its effect on peripheral resistance, thereby leading to less reflex activation of the sympathetic nervous and renin-angiotensin systems.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood; D004008:Diclofenac / Q000494:pharmacology; D004078:Dihydralazine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000031:analogs & derivatives*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D011188:Potassium / Q000097:blood / Q000652:urine; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000502:physiology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000652:urine
D002395:Catecholamines; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D004008:Diclofenac; D006830:Hydralazine; D012964:Sodium; D003404:Creatinine; D012083:Renin; D004078:Dihydralazine; D011188:Potassium