Age-related alterations in soluble guanylyl cyclase and cGMP pathway in spontaneously hypertensive rats.
BACKGROUND
Vascular contractility and blood pressure (BP) are regulated by soluble guanylyl cyclase (sGC) and cyclic guanosine monophosphate (cGMP) pathway, which can be influenced by heme oxygenase (HO)-derived carbon monoxide (CO). The age-related changes in sGC/cGMP pathway in tail artery smooth muscle cells (SMCs) in hypertension have not been systematically investigated.


METHODS
In the present study, spontaneously hypertensive rats (SHR) of 4, 8, and 20 weeks old were used. The basal and hemin-modulated levels of sGC and cGMP in tail artery tissues were examined.


RESULTS
Although BP of 20-week SHR was significantly elevated, sGC and cGMP levels were unaltered compared with age-matched Wistar-Kyoto rats (WKY). The levels of sGC and cGMP were significantly lower in 4- and 8-week SHR compared with age-matched WKY although BP of 4-week SHR was normotensive. Hemin administration resulted in a significant decrease in BP in 8-week (158.7 +/- 2.4 versus 123.5 +/- 1.3 mmHg, P < 0.01), but not in pre-hypertensive (4 weeks) or 20-week SHR or WKY at all ages. Coincidently, sGC and cGMP levels in 8-week SHRs were significantly elevated and so did the expression levels of HO-1. Hemin treatment did not increase the cyclic adenosine monophosphate (cAMP) content of tail artery from 8-week SHR. The constitutive HO-2 levels remained unchanged in 8- and 20-week SHR and age-matched WKY.


CONCLUSIONS
The HO-activity inhibitor, chromium mesoporphyrin, abolished the BP-lowering and HO- stimulating effects of hemin in young SHR. Our results suggest that alteration in sGC/cGMP pathway in vascular SMCs precedes the occurrence of hypertension but returns to normal once hypertension is fully manifested.
Ndisang
Joseph Fomusi
JF
Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada.
Wang
Rui
R
D000367:Age Factors; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D006162:Guanylate Cyclase; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D013623:Tail / Q000098:blood supply; D015854:Up-Regulation / Q000187:drug effects
D018160:Receptors, Cytoplasmic and Nuclear; D006427:Hemin; D000242:Cyclic AMP; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP