cGMP pathway and mechanical properties of carotid artery wall in WKY rats and SHR: role of endothelium.
We measured the static mechanical properties and tissue guanosine 3',5'-cyclic monophosphate (cGMP) content in the carotid artery of 16- to 18-wk-old Wistar-Kyoto (WKY) rats and age-matched spontaneously hypertensive rats (SHR). Carotid compliance (CC) and tissue cGMP measurements were performed under control conditions with intact endothelium (E+), after local incubation with methylene blue (10(-5) M, 20 min), and after mechanical removal of the endothelium (E-). Under control conditions, CC was lower in SHR than in WKY rats (P less than 0.01) and carotid cGMP level was higher in SHR than in WKY rats (30.34 +/- 3.69 vs. 19.72 +/- 2.28 fmol/mg tissue; P less than 0.02). Methylene blue induced no significant change in CC in both strains and produced a similar decrease in carotid cGMP in WKY rats by 88% (P less than 0.001) and in SHR by 94% (P less than 0.001). Endothelium removal induced a similar increase in CC relative to control conditions (P less than 0.01, in both strains) but reduced cGMP content by 28% in WKY rats (P less than 0.02) and by 90% in SHR (P less than 0.001), i.e., a significantly higher reduction in SHR than in WKY rats (P less than 0.001). Despite a higher vasomotor tone, the "cGMP pathway" seems to be more activated in the SHR than in the WKY rat. Our results suggest that the mechanism involved in cGMP synthesis regulation in the SHR is endothelium dependent. This may be interpreted as an insufficient endothelium-dependent compensatory phenomenon of local regulation against genetic abnormalities.
Mourlon-Le Grand
M C
MC
Institut National de la Santé et de la Recherche Médicale, Unité 141, Hôpital Lariboisière, Paris, France.
Benessiano
J
J
Levy
B I
BI
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D008751:Methylene Blue / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism* / Q000502:physiology; D011921:Rats, Inbred WKY / Q000378:metabolism* / Q000502:physiology; D014655:Vascular Resistance
D006152:Cyclic GMP; D008751:Methylene Blue