Prostacyclin and thromboxane A2 production in nitric oxide-deficient hypertension in vivo. Effects of high calcium diet and angiotensin receptor blockade.
The effects of chronic nitric oxide deficiency on prostacyclin and thromboxane A(2) production in vivo are unknown. Therefore, we treated rats with N(G)-nitro-L-arginine methyl ester (L-NAME), and used losartan and high calcium diet as antihypertensive treatments. Forty eight Wistar rats were divided into six groups: control; losartan (20mgkg(-1)day(-1)); high calcium diet (dietary calcium elevated from 1.1% to 3%); L-NAME (20mgkg(-1)day(-1)); losartan+L-NAME and high calcium diet+L-NAME. Prostacyclin and thromboxane A(2) production were measured after eight weeks as urinary 2,3-dinor-6-keto-PGF(1alpha) and 11-dehydro-TXB(2), respectively. Both the high calcium diet and losartan reduced blood pressure in L-NAME hypertension. Chronic nitric oxide deficiency did not modulate prostacyclin production but it nearly doubled thromboxane A(2) production in vivo. This effect was not influenced by lowering of blood pressure by blockade of angiotensin II type 1 receptors. Independent of the level of blood pressure and blockade of nitric oxide synthesis the high calcium diet decreased prostacyclin production by one third and increased thromboxane A(2) production almost two-fold in vivo.
Department of Internal Medicine, Tampere University Hospital, P.O. Box 2000, Tampere FIN-33521, Finland. bljual@uta.fi
Juha
J
Alanko
Pasi
P
Jolma
Peeter
P
Kööbi
Asko
A
Riutta
Jarkko
J
Kalliovalkama
Jari Petteri
JP
Tolvanen
Ilkka
I
Pörsti
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000627:therapeutic use; D002136:Calcium, Dietary / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D019808:Losartan / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002136:Calcium, Dietary; D004791:Enzyme Inhibitors; D011945:Receptors, Angiotensin; D009569:Nitric Oxide; D013928:Thromboxane A2; D011464:Epoprostenol; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester