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The Ca2" responsiveness of vascular smooth muscle myofilaments is not unique: it is increased during neuro-humoral activation and decreased during /3-adrenergic stimulation.In this study we tested whether an augmented Ca2" responsiveness of smooth muscle myofilaments may contribute to the increased coronary tone observed in hypertension using /3-escin-permeabilized coronary arteries from 3-mo-old stroke-prone spontaneously hypertensive rats (SHRSP) and their age matched normotensive reference strain (WKY rats). In intact coronary arteries, the response to 5-hydroxytryptamine (5-HT) but not to KCI was larger in SHRSP than in WKY rats. In (i-escin permeabilized coronary arteries in which the receptor effector coupling is still intact, 5-HT enhanced force at constant submaximal (Ca2") (pCa 6.38) to a greater extent in SHRSP. The Ca2" sensitizing effect of 5-HT was mimicked by GTPyS (0.01-10 IAM); again this effect was larger in SHRSP. In the absence of 5-HT or GTPyS the Ca2" force relation was similar in both groups. Forskolin induced relaxation at constant submaximal (Ca2"). This desensitizing effect was smaller in SHRSP than in WKY rats. In conclusion, this study shows that intracellular signalling pathways involved in modulating the Ca2" responsiveness of coronary smooth muscle myofilaments are altered in the genetically hypertensive animals favoring a hypercontractile state in the coronary circulation. (J. Clin. Invest. 1994Invest. . 94:1397Invest. -1403.) Key words: strokeprone spontaneously hypertensive rat . permeabilized coronary arteries *

G‐proteins may be involved in receptor‐mediated Ca2+‐sensitization of smooth muscle contraction, but the responsible G‐proteins are not yet known. Here we show that in β‐escin skinned mesenteric microarteries, H‐ras p21 proteins, preactivated with GTP or GTP γ S, increase force at constant submaximal Ca2+ (pCa 6.3) concentration dependently. The GTP‐bound form of the wild‐type H‐ras p21 and the oncogenic mutant (p21[G12V]) were equally effective. The nucleotide‐free and the inactive GDP‐bound form of ras p21 had no effect on force. The tyrosine kinase inhibitor, tyrphostin, partially reversed the effect of the ras proteins in the GTP‐bound form on force. Thus, ras proteins mimic the Ca2+‐sensitizing effect of GTPγS and vasoconstrictors in mesenteric microarteries which may involve tyrosine phosphorylation.

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The Operating Division of the Obstetric Compensation System of the Japan Council for Quality Health Care (JCQHC) will conduct a case-control study Note) with the aim of identifying causes of cerebral palsy (CP) and measures to prevent CP relapse by comparing affected cases compensated according to the Japan Obstetric Compensation System for Cerebral Palsy (JOCSC) with non-CP cases in the perinatal registry database of the Japan Society of Obstetrics and Gynecology (JSOG). The main study goals are to prevent the recurrence of