Male Gender and Not the Severity of Hypertension Is Associated With End-Organ Damage in Aged Stroke-Prone Spontaneously Hypertensive Rats

BACKGROUND: It is well-known that gender affects the progression of kidney failure. Male patients exhibit faster development of age-dependent renal disease than do women. In the present study, we examined arterial blood pressure (BP), proteinuria, and end-organ damage in male and female retired breeders from our colony of stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: Male (n = 7) and female (n = 11) SHRSP littermates maintained on Purina Laboratory Chow 5008 and water were studied starting at 53 weeks of age. Systolic BP was measured by tail-cuff plethysmography and 24-h urinary protein excretion was quantified while animals were housed in metabolic cages. Blood was obtained by retro-orbital bleeding. Mean arterial pressure (MAP) was then monitored by radiotelemetry. Organs were preserved for histopathologic assessment. RESULTS: Tail-cuff systolic BP did not differ between the sexes. Male SHRSP exhibited greater proteinuria (128 +/- 7 mg/d) than females (21 +/- 5 mg/d, P < .001). Blood urea nitrogen was higher in males (22 +/- 2 mg%) v females (15 +/- 1 mg%, P < .005). The MAP by radiotelemetry did not differ between the sexes (179 +/- 3 mm Hg in males v 192 +/- 6 mm Hg in females, 2 weeks after probe implantation). Stroke-related mortality was greater in males (83%) than females (10%). Renal vascular disease including thrombotic microangiopathy affecting glomeruli and microvessels and cardiac damage were more prominent in male SHRSP. CONCLUSIONS: These findings demonstrate that male gender is a major risk factor for multisystem end-organ damage associated with aging and hypertension in SHRSP, despite comparable degrees of hypertension among males and females.