No abstract

A C825T polymorphism was recently identified in the gene for the G-protein beta3 subunit, the T-allele being associated with hypertension. To better understand the underlying pathophysiological mechanisms, we compared the haemodynamics of young healthy males with and without the T-allele. In three studies, subjects were investigated with regard to cardiac and vascular function at rest and following intravenous administration of the beta-adrenoceptor antagonist, propranolol, and the alpha2-adrenoceptor agonist, alpha-methylnoradrenaline, and with regard to local venous vasoconstriction in the dorsal hand vein in situ following infusion of the alpha2-adrenoceptor agonist, azepexol. alpha2-Adrenoceptor agonists were chosen as vasoconstrictor drugs since alpha2-adrenoceptors couple to pertussis toxin (PTX)-sensitive G-proteins and since in-vitro studies have demonstrated enhanced signal transduction of PTX-dependent pathways in the presence of the T-allele. Total peripheral resistance was determined as a parameter of vasoconstrictor tone and heart rate, stroke volume and systolic time intervals for cardiac function. T-allele carriers had a significantly elevated stroke volume and lower total peripheral resistance at baseline. After propranolol, their fall in stroke volume was significantly greater. During alpha-methylnoradrenaline infusion, elevation of total peripheral resistance was not increased relative to controls. Similarly, the constriction response of the dorsal hand vein to azepexol was not different. Our study does not support the idea of increased vasoconstrictor tone in T-allele carriers either at rest or during stimulation of alpha2-adrenoceptors. However, this allele may be associated with elevated cardiac stroke volume.

Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway.

Background and Purpose-Research for infectious agents in the etiology of atherosclerosis has identified Chlamydia pneumoniae as a possible candidate. While there is evidence of an association between presence of this microorganism and atherosclerosis, it is unclear whether infection has a genuinely etiologic role in this disease, whether its presence influences clinical outcomes, and, if so, at which stages of disease this occurs. We have approached this issue in patients with advanced carotid artery atherosclerosis using molecular biological detection methods and clinically relevant indicators of pathology in carotid artery atheroma to determine whether the presence of C pneumoniae correlates with plaque instability. Methods-C pneumoniae was detected with the use of a sensitive nested polymerase chain reaction. Preoperative embolization and preoperative infarcts were recorded with the use of transcranial Doppler insonation of the middle cerebral artery and cerebral CT, respectively. Results-C pneumoniae DNA was detected in 25.5% of a cohort of 98 symptomatic patients. There was no significant difference in plaque stability as measured by embolization rates between the chlamydial-positive and -negative specimens. There was also no correlation between the number of ipsilateral hemispheric infarcts in the territory of the middle cerebral artery and chlamydial status. Conclusions-This study confirms that C pneumoniae is a common finding in atherosclerotic plaques of the carotid artery but suggests that the presence of the infectious organism has little detectable impact on plaque instability when measured by clinically significant markers. This raises important questions for the rationale of antibiotic therapy in atherosclerosis.

The accuracy of two-dimensional time-of-flight magnetic resonance angiography (MRA) in judging diameter narrowing of the extracranial carotid artery was studied using digital subtraction angiography (DSA) as the gold standard. Particular attention was paid to the specificity of the technique for 70–90% diameter stenoses. MRA and DSA examinations of 90 cervical carotid arteries were graded independently by 2 blinded readers. The examinations were compared in the categories 0–29, 30–69, 70–99 and 100% diameter narrowing (NASCET measurements). Overestimation of the degree of stenosis measured angiographically resulted in MRA sensitivity estimates of 77.8% for 0–29% angiographic stenosis and 31% for 30–69% angiographic stenosis. In the 70–99% stenosis group a false-positive rate of 21.9% resulted in 22 of 42 arteries being inappropriately placed in the high-grade stenosis group. In cases of 100% occlusion there was a false-negative rate of 35.7% (5 of 14 cases). MRA is reliable as a screening test for extracranial carotid occlusive disease. Limited ability of the technique to distinguish between ''surgical'' and ''non-surgical'' disease with inappropriate inclusion of some patients as potential surgical candidates limits its application as a single definitive pre-operative test.