Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

OBJECTIVE: Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). METHODS: We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 µm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. RESULTS: In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. CONCLUSIONS: Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

Gender differences in biomechanical properties of intramural coronary resistance arteries of rats, an in vitro microarteriographic study.

The prevalence of ischemic heart disease is lower in premenopausal females than in males of corresponding age. This should be related to gender differences in coronary functions. We tested whether biomechanical differences exist between intramural coronary resistance arteries of male and female rats. Intramural branches of the left anterior descending coronary artery (uniformly approximately 200microm in diameter) were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased from 2 to 90mmHg in steps and steady-state diameters were measured. Measurements were repeated in the presence of vasoconstrictor U46619 (10(-6)M) and the endothelial coronary vasodilator bradykinin (BK) (10(-6)M). Finally, passive diameters were recorded in calcium-free saline. A similar inner radius and a higher wall thickness (41.5+/-2.9microm vs. 31.4+/-2.7microm at 50mmHg in the passive condition, p<0.05) resulted in lower tangential wall stresses in male rats (18.9+/-1.9kPa vs. 24.9+/-2.5kPa at 50mmHg, p<0.05). Isobaric elastic modulus of vessels from male animals was significantly smaller at higher pressures. Vasoconstrictor response was significantly stronger in male than in female animals. Endothelial relaxations induced by BK were not different. This is the first demonstration that biomechanical characteristics of intramural coronary resistance arteries of a mammalian species are different in the male and female sexes. Higher wall thickness and higher vascular contractility in males are associated with similar endothelial function and larger high-pressure elasticity compared to females. These gender differences in biomechanics of coronary resistance arteries of rats may contribute to our better understanding the characteristic physiological and pathological differences in humans.

Intramural coronary artery constrictor reactivity to thromboxane is higher in male than in female rats.

BACKGROUND: The prevalence of cardiovascular disorders is higher among men than in age-matched women. This is probably related, in part, to gender-dependent differences in coronary function including thromboxane-A(2) (TXA(2)) sensitivity. This question has been examined only on major, epicardial coronaries. The intramural small arteries directly responsible for supplying the myocardial arterioles with blood have been hardly accessible for investigation, owing to difficulties in their preparation. Vasoconstrictor TXA(2) excess generated by platelets and the vascular wall may play an important role in coronary ischemic events. In the present study we tested the vasoconstrictor reactivity of intramural coronary arteries to TXA(2). METHODS: Secondary, intramural branches of the left anterior descendent coronary artery of Sprague-Dawley rats (diameter: 200 microm) were placed into a vessel chamber. TXA(2) vasoconstrictor reactivity was measured on the basis of pressure-diameter curves in normal Krebs-Ringer solution and after addition of TXA(2) receptor agonist. RESULTS: Vasoconstrictor response induced by TXA(2) agonist was twice as strong in males compared with females for the whole pressure range ( p < 0.001). CONCLUSIONS: A gender-dependent difference was demonstrated in TXA(2)-induced contraction of intramural coronary artery segments. In some pathologic situations the enhanced TXA(2) release from platelets and injured vascular wall may cause greater vasoconstriction of intramural coronary arteries in males than in females.

Estrogen replacement therapy reverses changes in intramural coronary resistance arteries caused by female sex hormone depletion.

OBJECTIVE: We tested the hypothesis that female sex hormone depletion and estradiol replacement therapy significantly influences the biomechanical properties of intramural coronary resistance arteries. DESIGN: Female rats (n=30) were divided into three groups. In group O, rats were subjected to bilateral ovariectomy. Group HRT was subjected to bilateral ovariectomy and estradiol replacement therapy. Rats in group C served as controls. One month after ovariectomy, intramural coronary arteries (approximately 200 microm in diameter) branching from the left anterior descending coronary were isolated, cannulated and studied by microarteriography. Intraluminal pressure was increased in steps between 0 and 90 mm Hg. The steady state diameter at each step was measured. These measurements were repeated in the presence of U46619, a thromboxane (TX) A2 receptor agonist (at a concentration of 10(-6) M), and bradykinin (BK; at 10(-6) M). Finally, Ca2+-free Krebs-induced passive diameter (PD) was measured in each group. RESULTS: Ovariectomy increased spontaneous myogenic tone of coronary arteries (p<0.05), which was normalized by estrogen replacement. Ovariectomy decreased distensibility observed at low pressure, although passive diameter was not changed. Estrogen replacement decreased wall stress and elastic modulus (p<0.05). The thromboxane A2 agonist induced the largest contraction in the ovariectomized group, whereas bradykinin-induced relaxation was the largest in the estrogen replacement group (p<0.05). CONCLUSION: Estradiol hormone replacement therapy (HRT) may exert a beneficial effect on myocardial perfusion in menopause by opposing the deterioration of biomechanical properties of intramural coronary resistance vessels induced by female sex hormone depletion.