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Objectives: To determine if estrogen acutely and directly alters arterial muscle relaxation, if estrogen is responsible for gender dichotomy in hypertension, and if arterial muscle from female spontaneously hypertensive rats (SHR) is slow to relax as is muscle from male SHR compared with arterial muscle of normotensive Wistar-Kyoto rats (WKY)., Methods: Relaxation rates of isometrically contracted arterial muscle from male rats were measured before and after addition of beta-estradiol. Blood pressure (BP) was monitored in intact male and female SHR and WKY and in ovariectomized and estrone-treated ovariectomized SHR and WKY. Relaxation rates of maximum isometric contractions of arterial muscle excised from male SHR and WKY and female SHR and WKY with varying chronic estrogen status were measured., Results: Beta-estradiol had no direct, acute effect on arterial muscle force or relaxation. Intact and estrone-implanted SHR females had significantly lower BP than males. Ovariectomized SHR developed high BP equivalent to that of males. Arterial relaxation was slower in both male and female SHR compared with WKY., Conclusions: Estrogen lowers BP in female SHR. Strain differences in relaxation rates are independent of gender and estrogen status. Estrogen has no effect on arterial muscle relaxation, suggesting another mechanism for the protective effect of estrogen in hypertension.

H(2)O(2)-induced pulmonary arterial smooth muscle (PASM) contractions are independent of Ca(2+) and myosin light chain phosphorylation. The purpose of this study was to determine whether mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1 and ERK2, or protein kinase C (PKC) activation is required for H(2)O(2)-induced contraction. Porcine PASM strips were stimulated with 1 mM H(2)O(2), 120 mM KCl, or 10 microM phorbol myristic acetate and freeze clamped at various times during the contractions. Changes in relative amounts of tyrosine/threonine phosphorylated MAPK compared with total MAPK were measured. MAPK tyrosine phosphorylation levels increased in correlation with tension development. However, 50 microM PD-98059, a MAPK/ERK kinase-MAPK kinase blocker, reduced MAPK phosphorylation below resting levels, even though the magnitude of the isometric tension development was unaltered. Freeze-clamped PASM strips were placed in a PKC activity assay buffer containing (32)P and CaCl(2) to measure the total myelin basic protein phosphorylation. The data show that: 1) the time courses of PKC activity and force produced in response to H(2)O(2) do not correlate, and 2) MAPK activation may be a concurrent event with, or a consequence of, tension development in response to a variety of agonists but is not responsible for contractions to H(2)O(2), high K(+), or phorbol esters.

One purpose of the current study was to establish whether vasoconstriction occurs in all vessel types in response to H(2)O(2). Isometric force was measured in pulmonary venous and arterial rings, and isobaric contractions were measured in mesenteric arteries and veins in response to H(2)O(2). A second purpose was to determine whether H(2)O(2)-induced contraction is calcium independent. The addition of H(2)O(2) to calcium-depleted (using the Ca(2+) ionophore ionomycin in zero calcium EGTA buffer) muscle caused contraction. Furthermore, permeabilized muscle contracted in response to H(2)O(2) even in zero Ca(2+). The final purpose was to determine whether the 20-kDa regulatory myosin light chain (MLC(20)) phosphorylation plays a role in H(2)O(2)-induced contraction. Pulmonary arterial strips were freeze-clamped at various time points during H(2)O(2)-induced contractions, and the relative amounts of phosphorylated MLC(20) were measured. H(2)O(2) caused dose-dependent contractions that were independent of MLC(20) phosphorylation. ML-9, a myosin light chain kinase inhibitor, had no effect on the H(2)O(2) contractile response. In conclusion, H(2)O(2) induces Ca(2+)- and MLC(20) phosphorylation-independent contraction in pulmonary and systemic arterial and venous smooth muscle.