LOVASTATIN REDUCES RENAL VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

We have reported that lovastatin attenuates the development of hyperte nsion in spontaneously hypertensive rats (SHR). The fall in arterial p ressure is associated with an elevation in renal medullary blood flow, normalization of the pressure-natriuresis relationship, and diminishe d hypertrophy of renal arterioles. However, the mechanism by which lov astatin alters renal vascular tone is unknown. The present study exami ned the effects of lovastatin on renal vascular tone and the expressio n of G proteins. Four-week-old SHR were chronically treated with lovas tatin (20 mg/kg/day) or vehicle by gavage for 4 weeks. At the end of t he study, mean arterial pressure averaged 131 +/- 4 (n = 5) and 160 +/ - 4 mm Hg (n 6) in lovastatin- and vehicle-treated SHR, respectively. Renal arterioles isolated from lovastatin-treated SHR were significant ly less responsive to norepinephrine and vasopressin than those obtain ed from vehicle-treated rats (ED50: 5.0 v 1.8 x 10(-7) mol/L for norep inephrine, and 8.0 v 5.2 x 10(-10) mol/L for vasopressin). The fall in renal vascular reactivity in lovastatin-treated SHR was associated wi th reduced levels of ras and rho proteins in renal arterioles, whereas the expressions of heterotrimeric G proteins (G(s), G(q), G(i)) were similar in renal arterioles from vehicle- and lovastatin-treated SHR. Overnight culture of renal arterioles with media containing lovastatin also diminished the expression of ras and rho proteins and the respon se to vasoconstrictors. These findings indicate that lovastatin dimini shes the response to vasoconstrictors and the expression of small G pr oteins in the renal vasculature of SHR and suggest that a fall in the levels of ras and rho proteins in these vessels may contribute to the antihypertensive effects of lovastatin. Am J Hypertens 1998;11:1222-12 31 (C) 1998 American Journal of Hypertension, Ltd.