In spontaneously hypertensive rats, antihypertensive therapy reduced myocardial stiffness, which was associated with improved collagen solubility rather than changes in total collagen.
Does antihypertensive therapy with hydralazine or captopril improve myocardial stiffness and collagen characteristics in spontaneously hypertensive rats?
Myocardial stiffness in hypertension is primarily driven by enhanced myocardial collagen cross-linking rather than increases in total collagen or type I phenotype concentrations.
p-value: p=<.01
BACKGROUND: The relative contributions of increases in myocardial collagen, collagen cross-linking, and the ratio of type I to type III collagen to the stiff myocardium in hypertension were determined. METHODS AND RESULTS: We compared the action of hydralazine (0.07 mmol x kg(-1) x d(-1)) with that of captopril (0.22 mmol x kg(-1) x d(-1)) on the left ventricular end-diastolic (LVED) myocardial stiffness constant, k (g x cm(-2)) and LV myocardial interstitial characteristics in spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) control rats. LVED k (SHR, 27.9+/-1; WKY, 19.5+/-1.2; P<.01), myocardial hydroxyproline concentrations (HPRO; microg/mg dry wt) (SHR, 4.19+/-0.16; WKY, 3.17+/-0.09; P<.001), and collagen type I/III ratios (SHR, 7.1+/-0.7; WKY, 2.1+/-0.2; P<.001) were increased, whereas the percentage of myocardial collagen extracted after cyanogen bromide digestion (an index of cross-linked collagen) was decreased (SHR, 17+/-3; WKY, 41+/-4; P<.001) in SHRs compared with WKY controls. Captopril therapy reduced LVED k, myocardial HPRO, collagen type I/III, and augmented collagen solubility (43+/-4) in SHRs to values similar to those measured in WKY controls. Hydralazine therapy, despite a favorable effect on LVED k in SHRs (20.+/-1.6, P<.01 compared with untreated SHRs), failed to influence either myocardial HPRO (4.18+/-0.18) or collagen type I/III (8+/-1) but did improve collagen solubility (31+/-2). CONCLUSIONS: An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.
Norton et al. (1997) studied Hypertension. Hydralazine and Captopril vs. Untreated SHRs and WKY controls was evaluated on Left ventricular end-diastolic (LVED) myocardial stiffness constant, k (p=<.01). In spontaneously hypertensive rats, antihypertensive therapy reduced myocardial stiffness, which was associated with improved collagen solubility rather than changes in total collagen.