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. CONCLUSION: 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.
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 hypertensiverats (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. CONCLUSION: 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.