Microvascular cell death in spontaneously hypertensive rats during experimental inflammation.
OBJECTIVE
Chronic hypertension is associated with an increased risk for tissue injury that may be mediated in part by endothelium and inflammatory cells. To clarify a possible underlying mechanisms, we examined leukocyte migration in the microcirculation and concomitant parenchymal cell death.


METHODS
The mesentery of spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar Kyoto (WKY) rats, was examined with digital fluorescence microscopy after topical stimulation with an inflammatory mediator (f-met-leu-phe, 10(-8)M). The migratory pathways of individual leukocytes were traced, and at the same time cell death was detected by use of a life-death indicator (propidium iodide) over a period of 3 hours.


RESULTS
Both WKY and SHR had a progressively increasing number of leukocytes migrating across the endothelium in postcapillary venules into the tissue parenchyma. But parenchymal cell death was detected in a random pattern in the mesentery tissue, without correlation to the migratory positions of the leukocytes. Although mature SHR rats (about 17 weeks) exhibited the same level of cell death as age-matched WKY rats, older WKY rats (about 30 weeks) had significantly lower levels of cell death, whereas the SHR rats maintained the same number of parenchymal cell death as mature animals.


CONCLUSIONS
These results suggest that in the presence of an inflammatory mediator, the SHR may exhibit a stronger response to an inflammatory mediator than normotensive WKY rats in a fashion that is age, but not blood pressure, dependent. Parenchymal cell death does not correlate with migration of activated leukocytes at the microvascular level.
Mun
Kyo C
KC
Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego La Jolla, CA 92093-0412, USA.
Delano
Frank A
FA
Tran
Edward D
ED
Schmid-Schönbein
Geert W
GW
D000367:Age Factors; D000818:Animals; D016923:Cell Death; D002634:Chemotaxis, Leukocyte; D006973:Hypertension / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008643:Mesentery / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D008833:Microcirculation / Q000473:pathology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013152:Splanchnic Circulation
D009240:N-Formylmethionine Leucyl-Phenylalanine