Prostacyclin and thromboxane A2 production in nitric oxide-deficient hypertension in vivo. Effects of high calcium diet and angiotensin receptor blockade

Abstract

The effects of chronic nitric oxide deficiency on prostacyclin and thromboxane A₂ 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 (20 mg kg⁻¹ day⁻¹); high calcium diet (dietary calcium elevated from 1.1% to 3%); L-NAME (20 mg kg⁻¹ day⁻¹); losartan+L-NAME and high calcium diet+L-NAME. Prostacyclin and thromboxane A₂ production were measured after eight weeks as urinary 2,3-dinor-6-keto-PGF_1α and 11-dehydro-TXB₂, 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 A₂ 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 A₂ production almost two-fold in vivo.