We tested the hypothesis that plasma brain natriuretic peptide (BNP) levels are elevated in patients with acute cerebrovascular diseases (CVD) independent of heart disease, and reflect CVD severity. After careful evaluations for heart disease, the study included 79 consecutive patients with CVD without any evidence of heart disease admitted within 48 h after onset (71 ± 10 years), and 26 control subjects without CVD (CT,

CF6 causes hypertension by directly enhancing Ca2+ signalling in VSMCs and vasoconstriction in the mesenteric arteriolar network via c-Src activation.

Background-We reported that phospholipase C (PLC)-␦1 activity was enhanced 3-fold in patients with coronary spastic angina. We detected variant PLC-␦1 with replacement of arginine 257 by histidine (R257H) showing increased enzymatic activity. We tested the hypothesis that increased PLC-␦1 activity causes enhanced coronary vasomotility. Methods and Results-We generated transgenic (TG) mice with human R257H variant PLC-␦1 in vascular smooth muscle cells. PLC enzymatic activity in the coronary artery was increased by 2.57 and 1.89 times, respectively, in homozygous and heterozygous TG compared with wild-type (WT) mice. ST elevation after ergometrine occurred in 17 of 18 homozygous TG, 6 of 20 heterozygous TG, and 3 of 22 WT mice (PϽ0.01, homozygous TG versus WT; PϽ0.05, homozygous TG versus heterozygous TG; PϭNS, heterozygous TG versus WT). ST elevation was associated with bradyarrhythmias in homozygous TG mice. Focal coronary artery narrowing was documented with the microvascular filling technique in 3 of 5 homozygous TG mice after ergometrine but not in any of 7 WT mice (PϽ0.05). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in homozygous TG mice (PϽ0.01) but not in heterozygous TG or WT mice. Coronary perfusion pressure increase after prostaglandin F 2␣ was similar among homozygous TG, heterozygous TG, and WT mice. Cultured rat aortic smooth muscle cells transfected with variant PLC-␦1 showed a higher PLC activity than those with WT PLC-␦1 (PϽ0.05) and furthermore showed greater intracellular Ca 2ϩ response to acetylcholine in variant than in WT PLC-␦1 (PϽ0.05). Conclusions-Increased PLC-␦1 activity enhances coronary vasomotility such as that seen in patients with coronary spastic angina.