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L-NAME-induced protein remodeling and fibrosis in the rat heart
O Pechánová1, I Bernátová, V Pelouch
1Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. pechan@unpf.savba.sk
Insights
Nitric oxide (NO) deficiency, not elevated blood pressure, drives heart remodeling in L-NAME-induced hypertension. This NO deficiency promotes fibrotic tissue growth in the left ventricle, impacting cardiac protein structure.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Pathology
Background:
- Hypertension is associated with cardiac remodeling.
- Nitric oxide (NO) plays a crucial role in cardiovascular homeostasis.
- Long-term inhibition of NO synthesis can induce hypertension and cardiac changes.
Purpose of the Study:
- To investigate whether NO deficiency or elevated systolic blood pressure (SBP) is responsible for cardiac protein and structural remodeling in L-NAME-induced hypertension.
- To elucidate the specific roles of NO deficiency and hemodynamic changes in collagenous protein and fibrotic tissue alterations in the left ventricle.
Main Methods:
- Rats were treated with varying doses of N(G)-nitro-L-arginine methyl ester (L-NAME) to induce hypertension.
- Systolic blood pressure (SBP), NO synthase activity, and cGMP concentration in the left ventricle were measured.
- Protein profiles, collagen content (hydroxyproline), and myocardial fibrosis were assessed.
Main Results:
- L-NAME treatment increased SBP similarly in both tested groups.
- NO synthase activity and cGMP levels decreased in a dose-dependent manner with L-NAME administration.
- Increased collagen and myocardial fibrosis were observed, particularly in the higher L-NAME dose group, correlating with NO deficiency.
Conclusions:
- NO deficiency, rather than elevated SBP, is the primary driver of collagenous protein and fibrotic tissue changes in the left ventricle during L-NAME-induced hypertension.
- The extent of fibrotic tissue growth is proportional to the administered L-NAME dose, highlighting the critical role of NO.
- These findings suggest NO deficiency directly contributes to adverse cardiac remodeling in hypertensive states.
Abstract:
The aim of the present study was to determine whether NO deficiency itself or rather the elevation of systolic blood pressure is responsible for the protein and structural remodeling of the heart during hypertension induced by long-term treatment by nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Three groups of rats were investigated. The first group served as control. In the second group L-NAME was given in the dose of 20 mg/kg/day in the drinking water and in the third group L-NAME was given in the dose of 40 mg/kg/day during 4 weeks. While L-NAME treatment in both doses caused essentially the same increase in systolic blood pressure (SBP), NO synthase activity and cGMP concentration in the left ventricle decreased by 17% and 13%, respectively in the 20 mg/kg/day L-NAME group and by 69% and 27%, respectively in the 40 mg/kg/day L-NAME group. The protein profile of the left ventricle in both L-NAME groups was characterized by an increased concentration of metabolic proteins. Nevertheless, a significant increase in the concentration of pepsin-soluble collagenous proteins and the concentration of hydroxyproline in pepsin-insoluble collagenous proteins was found only in the group receiving 40 mg/kg/day L-NAME. The morphometric evaluation revealed a significant increase in myocardial fibrosis in both L-NAME groups. However, this was more pronounced in the 40 mg/kg/day L-NAME group. It is concluded that NO deficiency resulted in significant enhancement of fibrotic tissue growth in proportion to the administered L-NAME dose, while SBP was increased similarly in both L-NAME groups. Thus, NO deficiency rather than hemodynamic changes appears to be crucially involved in collagenous protein and fibrotic tissue changes of the left ventricle in hypertension induced by L-NAME.