Effects of angiotensin II on remodelling of the airway and the vasculature in the rat.
Airway remodelling occurs in chronic asthma. Angiotensin II promotes growth in cardiovascular remodelling. Since the renin-angiotensin system is activated in acute severe asthma, we hypothesized that angiotensin II has a role in airway remodelling. A total of 14 young male Wistar rats were randomly divided into two groups. All received 2-week infusions of bromodeoxyuridine, and the experimental group also received angiotensin II. Blood pressure rose in the angiotensin II-infused group [mean levels: pre-infusion, 134.9 (S.D. 14.7) mmHg; post-infusion, 197.1 (22.5) mmHg], and expression of renin mRNA in the renal juxtaglomerular cells was suppressed in these animals. The proportion of bromodeoxyuridine-positive cell nuclei was no different in the airways of control and angiotensin II-infused animals for smooth muscle [mean bromodeoxyuridine index: control, 8. 6% (S.E.M. 1.1%); angiotensin II, 9.3% (1.1%)], epithelium [control, 16.7% (2.3%); angiotensin II, 16.0% (2.2%)] and adventitia [control, 26.4% (2.2%); angiotensin II, 26.6% (2.4%)]. In the arteries, bromodeoxyuridine indices were higher in the angiotensin II-infused rats [18.4% (2.3%)] than in the control animals [9.4% (2.8%)], but no difference was found in the veins [12% (2.9%) and 11.4% (2.6%) respectively]. Morphometry of the airway wall and mesenteric vasculature was no different in the two groups. Therefore a 2-week infusion of angiotensin II increases blood pressure and DNA synthesis in the mesenteric arteries, but does not cause airway remodelling, in the rat.
Ramsay
S G
SG
Department of Respiratory Medicine, West Glasgow Hospitals University NHS Trust, Glasgow, Scotland, U.K. SGRamsay@aol.com
Kenyon
C J
CJ
Whyte
N
N
McKay
I C
IC
Thomson
N C
NC
Lindop
G B
GB
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000032:analysis / Q000097:blood; D018709:Statistics, Nonparametric; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000963:Antimetabolites; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D004247:DNA; D012083:Renin; D001973:Bromodeoxyuridine