cyclic-gmp and Cerebral-Hemorrhage

Collagen type IV is the major structural component of the basement membrane and COL4A1 mutations cause adult small vessel disease, familial porencephaly and hereditary angiopathy with nephropathy aneurysm and cramps (HANAC) syndrome. Here, we show that animals with a Col4a1 missense mutation (Col4a1(+/Raw)) display focal detachment of the endothelium from the media and age-dependent defects in vascular function including a reduced response to nor-epinephrine. Age-dependent hypersensitivity to acetylcholine is abolished by inhibition of nitric oxide synthase (NOS) activity, indicating that Col4a1 mutations affect vasorelaxation mediated by endothelium-derived nitric oxide (NO). These defects are associated with a reduction in basal NOS activity and the development of heightened NO sensitivity of the smooth muscle. The vascular function defects are physiologically relevant as they maintain in part the hypotension in mutant animals, which is primarily associated with a reduced red blood cell volume due to a reduction in red blood cell number, rather than defects in kidney function. To understand the molecular mechanism underlying these vascular defects, we examined the deposition of collagen type IV in the basement membrane, and found it to be defective. Interestingly, this mutation also leads to activation of the unfolded protein response. In summary, our results indicate that mutations in COL4A1 result in a complex vascular phenotype encompassing defects in maintenance of vascular tone, endothelial cell function and blood pressure regulation.

Topics: Animals; Animals, Newborn; Blood Vessels; Cerebral Hemorrhage; Collagen Type IV; Cyclic GMP; Endothelial Cells; Erythrocyte Volume; Homeostasis; Hypotension; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Muscle, Smooth, Vascular; Mutation; Nitric Oxide; Nitric Oxide Synthase; Unfolded Protein Response; Vasodilation

Topics: Cerebral Arteries; Cerebral Hemorrhage; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Humans; Hypertension; Internal Capsule; Magnetic Resonance Imaging; Male; Middle Aged; Paresis; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Recovery of Function; Sildenafil Citrate; Sulfones; Thalamus; Tomography, X-Ray Computed; Vasodilation; Vasodilator Agents

Topics: Brain; Cerebral Hemorrhage; Cyclic GMP; Homeostasis; Humans; Infant, Newborn; Nitric Oxide

A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome.. Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide-induced impairment of cerebral autoregulation plays a role here.

Topics: Cerebral Hemorrhage; Cyclic GMP; Homeostasis; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Logistic Models; Nitric Oxide

The multiple experimental parameters of different aspects in this study were determined in the patients with "Liver Yang Forming Wind Syndrome (LYFWS)", "Qi Deficiency Blood Stagnation Syndrome (QDBSS)" and "Yin Deficiency Forming Wind Syndrome (YDFWS)". The results showed that cerebral hemorrhage was similar to cerebral infarction in almost all parameters and the two diseases were with LYFWS. It was found that there were several characteristics in LYFWS, i.e. 1. Hyperfunction of sympathetic adrenal medullary system. 2. Hypotriiodothyroidoglobulin syndrome. 3. The marked changes of the active substance regulating vessel smooth muscle function. 4. The increased inflammatory medicators. The pathophysiological parameters in patients with QDBSS were the same as those with YDFWS, but the changes of QDBSS and YDFWS weRe milder than those of LYFWS.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Cerebral Hemorrhage; Cerebral Infarction; Cyclic AMP; Cyclic GMP; Diagnosis, Differential; Female; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Norepinephrine; Thromboxane B2

A previous study showed that cerebrospinal fluid from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure contains 15 to 30 nm 3', 5' cyclic adenosine monophosphate. We measured the concentration of this cyclic nucleotide by radioimmunoassay in cerebrospinal fluid from the lateral ventricle of six patients with prolonged coma (20 days or longer) after head trauma (four), or spontaneous intracranial hemorrhage (two). Coma was graded IV to I in order of decreasing severity. Fluid was removed at intervals of six to 72 hours from a Rickham reservoir placed in the lateral ventricle. Concentration of the cyclic nucleotide (mean +/- S.E.M.) in coma of Grades IV, III, II and I was 2.1 +/- 0.3, 4.6 +/- 0.5, 6.3 +/- 1.4 and 12.5 +/- 2.4 nM respectively. After sensorium became normal, cAMP was 21.0 +/- 1.4 nM. Correlation between grade of coma and concentration was -0.89 (P less than 0.01). Thus, prolonged coma appears to be associated with a disturbance of cyclic AMP metabolism within the central nervous system.

Topics: Adult; Cerebral Hemorrhage; Cerebral Ventricles; Coma; Craniocerebral Trauma; Cyclic AMP; Cyclic GMP; Female; Humans; Intracranial Pressure; Male; Middle Aged; Time Factors; Unconsciousness