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.