1992 年 15 巻 1 号 p. 3-10
The concept of volume and vasoconstriction as polar elements in a model of the pathogenesis of hypertension has proven to be very useful. Many lines of investigation also suggest that the kidney must be involved in sustaining hypertension, whatever the primary pathogenetic mechanism. There are few studies, however, to link the status of renal perfusion and function to models of vasoconstriction and volume. We assessed the renal vascular (electromagnetic flowmeter) and depressor responses to two classes of agent, manidipine (a calcium antagonist) and enalaprilat (an ACE inhibitor), in rats with two models of hypertension. The spontaneously hypertensive rat (SHR) in comparison to its genetic mate, the normotensive WKY, was studied as a model in which vasoconstriction dominates pathogenesis. DOCA-salt hypertension was induced in rats as a model of volume-dependent hypertension. In SHR and WKY, enalaprilat and manidipine induced similar depressor responses and similar renal vasodilatation: internal evidence suggested that enalaprilat acted primarily by reducing angiotensin II (All) formation. The similarity of the response to manidipine may reflect its ability to block renal vasoconstriction induced by All. In the DOCA-salt model, on the other hand, manidipine was much more effective both as a depressor agent and as a renal vasodilator than enalaprilat. Indeed, the renal vasodilatation induced by manidipine in the DOCA-salt model exceeded substantially the vasodilatation induced by either class of agent in SHR. The results are consistent with an action of manidipine in the volume-dependent model that reverses the action of an agent that leads to increased vascular smooth muscle intracellular calcium -perhaps the digitalis-like factor. We conclude that quantitatively important renal vascular changes occur in both models of volume and vasoconstriction, and that the model determines the renal response to calcium antagonists and ACE inhibitors. (Hypertens Res 1992; 15: 3-11)
