Antihypertensive action of heparin: role of the renin-angiotensin aldosterone system and prostaglandins.
Chronic subcutaneous administration of heparin consistently lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Groups of spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats were treated with subcutaneous heparin (700 U/d) for 6 weeks. Weekly determinations of systolic blood pressure (tail-cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins (PGs) (PGF2 alpha, PGI2), thromboxane A2, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II, and norepinephrine, were determined. As before, heparin produced a significant (P < .01) decrease in hematocrit in both SHRs and NWRs, but a parallel decrease in blood pressure was noted only in SHRs. A significant (P < .001) increase in plasma renin activity was found in heparin-treated SHRs and NWRs; however, a corresponding elevation of plasma aldosterone level was noted only in heparin-treated NWR. Plasma aldosterone level significantly (P < .01) decreased in heparin-treated SHRs. Plasma PGs and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoconstrictor substances were essentially similar among the heparin-treated and control groups. These findings suggest that PGs or kallikrein have a slight or no role in determining the antihypertensive effect of heparin. Conversely, the results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism of heparin.
Susic
D
D
Institute for Medical Research, Belgrade, Yugoslavia.
Mandal
A K
AK
Jovovic
D
D
Stojanov
M
M
Djordjevic-Denic
G
G
Kentera
D
D
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015237:Dinoprost / Q000097:blood; D011464:Epoprostenol / Q000097:blood; D006400:Hematocrit; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000652:urine; D011453:Prostaglandins / Q000097:blood*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013928:Thromboxane A2 / Q000097:blood
D011453:Prostaglandins; D000450:Aldosterone; D013928:Thromboxane A2; D006493:Heparin; D015237:Dinoprost; D011464:Epoprostenol; D007610:Kallikreins