Lovastatin reduces renal vascular reactivity in spontaneously hypertensive rats.
We have reported that lovastatin attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The fall in arterial pressure is associated with an elevation in renal medullary blood flow, normalization of the pressure-natriuresis relationship, and diminished hypertrophy of renal arterioles. However, the mechanism by which lovastatin alters renal vascular tone is unknown. The present study examined the effects of lovastatin on renal vascular tone and the expression of G proteins. Four-week-old SHR were chronically treated with lovastatin (20 mg/kg/day) or vehicle by gavage for 4 weeks. At the end of the 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 significantly less responsive to norepinephrine and vasopressin than those obtained from vehicle-treated rats (ED50: 5.0 v 1.8 x 10(-7) mol/L for norepinephrine, 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 with reduced levels of ras and rho proteins in renal arterioles, whereas the expressions of heterotrimeric G proteins (Gs Gq, Gi) 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 response to vasoconstrictors. These findings indicate that lovastatin diminishes the response to vasoconstrictors and the expression of small G proteins 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.
Jiang
J
J
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Sun
C W
CW
Alonso-Galicia
M
M
Roman
R J
RJ
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008148:Lovastatin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D008148:Lovastatin; D019204:GTP-Binding Proteins; D009638:Norepinephrine