Abstract-Kidney function is critical in determining the level of arterial pressure and in the pathogenesis of hypertension.Important evidence comes from studies in which the level of blood pressure is dictated by the donor when kidneys are transplanted between genetically hypertensive and normotensive rats. We have hypothesized that pharmacotherapy modifies specific properties of the kidney, particularly the vasculature, such that after kidney transplantation, there are persistent changes in the level of arterial pressure. Consistent with previous studies, a 2-week aggressive treatment of adult (15 weeks) spontaneously hypertensive rats with an angiotensin-converting enzyme inhibitor (enalapril) combined with a low-salt diet induced a persistent change in the kidney and a decrease in arterial pressure (18%). These persistent changes in arterial pressure could be completely transferred to untreated adult spontaneously hypertensive rats by kidney transplantation (ie, pressure in untreated rats was decreased after transplantation of a kidney donated from a previously treated rat). Further, the importance of kidney-specific changes was demonstrated by finding that the treatment-induced lowering of arterial pressure was completely reversed by transferring an untreated kidney into a previously treated rat.The specific treatment-induced changes to the kidney included a decrease in structurally based renal vascular resistance that was similar to the persistent lowering of arterial pressure. These data provide evidence for a link between the treatment-induced changes in kidney vascular structure and the persistent lowering of arterial pressure. The findings also suggest that a key pharmacotherapeutic target in hypertension should be kidney-specific changes, such as renal vascular structure.

Abstract-The kidney plays a critical role in regulating the level of arterial pressure and in the pathogenesis of hypertension. Important evidence has come from studies in which hypertension is generated by transplanting kidneys from genetically hypertensive rats into normotensive recipients, suggesting that the level of blood pressure is strongly influenced by the genetic background of the kidney. We hypothesized that pharmacotherapy could modify specific properties intrinsic to the kidney such that after transplantation, there would be persistent changes in the level of arterial pressure. We determined that angiotensin-converting enzyme inhibitor treatment (enalapril) in spontaneously hypertensive rats induced both a persistent 17% reduction of mean arterial pressure and a persistent change in the kidney. This persistent change in the circulation could be completely transferred to untreated spontaneously hypertensive rats by kidney transplantation; ie, mean arterial pressure in untreated spontaneously hypertensive rat recipients was persistently lowered after transplantation of a kidney from a previously treated spontaneously hypertensive rat donor. In addition, the persistent lowering of mean arterial pressure after enalapril treatment could be completely abolished by implanting an untreated kidney, thereby revealing the importance of the kidney-specific changes. Furthermore, after within-group transplantations, there were no changes in the level of arterial pressure; ie, a 16% difference in mean arterial pressure remained between the 2 groups. The findings revealed that drug-induced changes specific to the kidney determined the level of arterial pressure, thereby suggesting the kidney should be a key therapeutic target for pharmacotherapy. Key Words: transplantation, renal Ⅲ renin-angiotensin system Ⅲ rats, spontaneously hypertensive Ⅲ arterial pressure Ⅲ angiotensin-converting enzyme inhibitors A ccording to a model of the circulation proposed by Guyton, 1 regulation of arterial pressure occurs at a level that permits fluid balance to be achieved. Specifically, this conceptual framework emphasizes that the kidneys are critical in regulating sodium and water balance and the long-term level of arterial pressure. In part, the operating range of arterial pressure is determined by the pressure-natriuresis mechanism, a process in which there is a direct relation between arterial pressure and urinary sodium excretion. Resetting of this relation to higher levels has been proposed to be a principle cause of hypertension, particularly in spontaneously hypertensive rats (SHR). 1,2 Studies by Folkow and others [3][4][5][6] have suggested that differences in vascular structure underlie some of the circulatory alterations in SHR, such as the shift in the operating range of the pressurenatriuresis mechanism. 7 Regardless of the mechanism, the kidneys of SHR have been shown to have a transplantable, genetically determined abnormality that confers the donor's increased level of arterial pressure onto the circulation of the ...

Aggressive antihypertensive treatments may be more beneficial in improving erectile function in aged SHR, via an effect that appears to be tissue specific, and not based on changes in blood pressure.