Increased incidence and severity of polyarteritis nodosa in reproductive senescent female spontaneously hypertensive stroke-prone rats (SHRSP)

Epidemiological studies suggest that the risk of developing several vascular disorders increases after menopause. This increased risk may be associated with the loss of the protective effects of estrogen in the vasculature. We hypothesize that the increased incidence and severity of polyarteritis noitosa (PAN) in female SHRSP is associated with reproductive senescence. The vasculature of the gastrointestinal (GI) tract was examined for vasculitic lesions in necropsied SHRSP and Wistar-Kyoto normotensive rats. The age range of the rats was from 3-18 months. The presence of arterial lesions were characterized by microscopic appearance. Lesion severity was based upon distribution and graded on a scale of 1 to 4 ; 1= absent: 2= duodenal arteries; 3= duodenal + jejunal arteries; and 4= arteries along the entire gut. The earliest detection of the disease occurred at approximately 10-12 months of age. In age matched animals, PAN was present in 24% of the SHRSP males (n=123) and 87% of the SHRSP females (n=I7I). None of the WKY animals had the vascular disease (n=373), suggesting that hypertension increases the risk for its development. In those males with PAN, 70, 30 and 10% were graded 2, 3 and 4. respectively. However, in females 8, 15 and 67%. were graded 2, 3 and 4, respectively. These observations indicate that inflammatory responses in arteries of SHRSP are age-related and occur with greater incidence and severity in females. The age of SHRSP at the time of the development of PAN in females coincides with reproductive senescence (∼10-12 months of age).