Remodelling of mesenteric arteries in genetically hypertensive rats cross-fostered from birth to normotensive Wistar rats.
1. The effects of cross-fostering genetically hypertensive (GH) with normotensive (N) Wistar rats on the structure of mesenteric resistance arteries (MRA) in young (6 week old) and adult (18 week old) rats were investigated to see whether the abnormal remodelling known to exist in GH rats could be prevented by changing the maternal environment. 2. Genetically hypertensive and normotensive rat pups were reared either by their natural mothers or a foster mother of the opposite strain (NX and GHX) with fostering done within 24 h of birth. 3. Blood pressure (BP) was measured from age 6-18 weeks; at 6 and 18 weeks MRA structure was assessed. 4. At the time of death, intra-arterial mean BP was measured (via the femoral artery), after which MRA were fixed by perfusion (at the systolic BP of the rat) via the abdominal aorta, first with 75% Tyrode's solution containing heparin and papaverine, followed by 2% glutaraldehyde in 75% Tyrode's solution. Arteries were dissected out, processed and embedded in Technovit (Heraeus Kulzer, Werheim, Germany) and serial sections were cut and stained with Giemsa. 5. Stereological techniques were used to determine media width, lumen diameter and medial cross-sectional area (CSA); in addition, the ratio of media width to lumen diameter was calculated. Smooth muscle cell density was also calculated. 6. In MRA from 6-week-old rats, GH rats compared with N rats had increased media width and CSA and an increased ratio of media width to lumen diameter. 7. There were no significant changes in structure in the GHX group compared with GH rats. The NX group compared with N rats had increased media width and CSA and lumen diameter, but no change in the ratio of media width to lumen diameter. Smooth muscle cell density, reduced in GH compared with N rats, was increased (P < 0.001) in the NX group, but not changed in the GHX group compared with GH rats. 8. In 18-week-old GH rats compared with N rats, the MRA had a decreased media width and medial CSA and smaller lumen diameter, but there was no change in the ratio of media width to lumen diameter. 9. In the GHX group compared with GH rats, media width and CSA were reduced; in the NX group compared with N rats, media width was increased, lumen decreased and the ratio of media width to lumen diameter increased. Smooth muscle cell density was increased (P < 0.001) in the GHX group, but not in the NX group. 10. Changing the maternal environment significantly affected BP in GHX and NX groups up to 9-10 weeks of age but, in adult rats, the BP differences were no longer present. Thus, structural changes were seen at 6 weeks of age in MRA from NX rats and also at 18 weeks in GHX and NX rats (even though the BP differences were no longer significant); structural remodelling occurred independently of BP.
Ledingham
Janet M
JM
Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago, Dunedin, New Zealand. janet.ledingham@stonebow.otago.ac.nz
Ashton
Nick
N
D000822:Animal Husbandry / Q000379:methods*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013997:Time Factors; D014655:Vascular Resistance