Brain stem control of arterial pressure in chronic arterial baroreceptor-denervated rats

Interruption of the baroreceptor reflex by transection of afferent nerves (sinoaortic denervation; SAD) or lesions of nucleus tractus solitarius (NTS) elevates sympathetic nerve activity (SNA) and arterial pressure (AP). However, within 1 wk, mean AP returns to normal despite the absence of baroreflexes. In this study, we examine central mechanisms that control AP in chronic baroreceptor-denervated rats. In urethane-anesthetized rats (1.5 g/kg i.v.) after autonomic ganglionic blockade (5 mg/kg i.v. chlorisondamine), alpha1-adrenergic-mediated pressor responses (1-100 microg/kg i.v. phenylephrine) were not altered by chronic lesions of NTS, indicating vascular reactivity to sympathetic stimulation is normal. Transection of the spinal cord at T1 profoundly decreased AP and was not further reduced by chlorisondamine in control or denervated rats. Inhibition of the rostral ventrolateral medulla (RVLM) by microinjections of muscimol (100 pmol/side) decreased AP to levels not further reduced by chlorisondamine in control rats, rats with SAD, and rats with NTS lesions. Blockade of GABA(A) receptors in the RVLM (50 pmol/side bicuculline) increased AP similarly in control rats and denervated rats. In agreement, inhibition of the caudal ventrolateral medulla (CVLM) by microinjections of muscimol or blockade of glutamatergic inputs (2.7 nmol/side kynurenate) produced comparable increases in AP in control and denervated rats. These data suggest the RVLM continues to drive the SNA that regulates AP in the chronic absence of baroreceptor inputs. In addition, despite the absence of a tonic excitatory input from NTS, in chronic baroreceptor-denervated rats glutamatergic inputs drive the CVLM to tonically inhibit the RVLM. Baroreceptor-independent regulation of the ventrolateral medulla may underlie central mechanisms contributing to the long-term control of AP.     

Nonsymmetrical bifurcations in arterial branching

The results of optimality studies of the branching angles of arterial bifurcations are extended to nonsymmetrical bifurcations. Predicted nonsymmetrical bifurcations are found to be not unlike those observed in the cardiovascular system.     

Age-related arterial calcification in rats

In man, i) arteries calcify with age and ii) age-linked arterial calcification is amplified by vascular pathology such as hypertension or arteriosclerosis. Age-linked arterial calcification has a bad prognosis but drugs to prevent it are lacking. This is partially due to the lack of appropriate animal models. This paper looks at the extent to which arteries calcify with age in the rat and whether hypertension or arteriosclerosis amplifies such calcification. Total calcium levels were determined by acid digestion and flame spectrophotometry and intracellular calcium levels ([Ca2+]i) by the intracellular calcium-sensitive dye, fura-2. Arteries contained up to 5 times more calcium than other soft tissues. Arteries progressively calcified with age whereas other soft tissues did not. Accumulation of calcium with age was essentially extracellular. Hypertension had no effect on age-related arterial calcification. Calcification of the same order as in man was produced in a rat model of arteriosclerosis (vitamin D plus nicotine treatment). In conclusion, as in man, age-linked, organ-specific arterial calcification does occur in rats but its intensity is far less. Arterial calcification of a similar degree to that observed in man can be obtained in rats by hypervitaminosis D plus nicotine.     

Optimality principles in arterial branching

A comparative study of four optimality principles for the branching geometry of blood arteries is presented. The results offer four different criteria which can be tested by experimental data to establish which of these principles is followed in the cardiovascular system. More significantly, the results suggest the further possibility that the geometry of arterial junctions may be governed by all of these principles simultaneously, to thus achieve a much higher degree of optimality than has hitherto been suspected. This result offers a basis for seeking a correlation between the degree of optimality of a particular junction and the incidence of certain arterial lesions at that junction.     

Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension

Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P_pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P_pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.     

Relation of effective arterial elastance to arterial system properties

Effective arterial elastance (E(a)), defined as the ratio of left ventricular (LV) end-systolic pressure and stroke volume, lumps the steady and pulsatile components of the arterial load in a concise way. Combined with E(max), the slope of the LV end-systolic pressure-volume relation, E(a)/E(max) has been used to assess heart-arterial coupling. A mathematical heart-arterial interaction model was used to study the effects of changes in peripheral resistance (R; 0.6-1.8 mmHg x ml(-1) x s) and total arterial compliance (C; 0.5-2.0 ml/mmHg) covering the human pathophysiological range. E(a), E(a)/E(max,) LV stroke work, and hydraulic power were calculated for all conditions. Multiple-linear regression analysis revealed a linear relation between E(a), R/T (where T is cycle length), and 1/C: E(a) = -0.13 + 1.02R/T + 0.31/C, indicating that R/T contributes about three times more to E(a) than arterial stiffness (1/C). It is demonstrated that different pathophysiological combinations of R and C may lead to the same E(a) and E(a)/E(max) but can result in differences of 10% in stroke work and 50% in maximal power.     

Small disturbance in arterial blood flow

The behaviour of a small disturbance in an arterial blood flow has been studied analytically. The growth equation governing growth or decay of a disturbance has been obtained and solved. The behaviour of wave amplitude has been investigated as the wave propagates in time. The application of results to the human arterial system shows that the shock waves are not expected under normal physiological conditions. In the case of a pathologically increased pressure rise at the root of aorta, shock-like transitions may develop in the periphery. It is observed that the friction effects are to resist the tendency of shock formation in arteries.     

Role of zinc in regulation of arterial blood pressure and in the etiopathogenesis of arterial hypertension

Increased gastrointestinal absorption and urinary excretion of zinc has been confirmed in experimental and clinical studies on primary arterial hypertension as a result from changes of intracellular and extracellular zinc content. In arterial hypertension, the levels of zinc in serum, lymphocyte, and bone decrease while increasing in heart, erythrocytes, kidney, liver, suprarenal glands and spleen. These changes result in the loss of zinc homeostasis that leads to various degrees of deficiency, not entirely compensated by nutritional factors or increased absorption in the gastrointestinal tract. Loss of zinc homeostasis can be both cause and effect of high blood pressure. In the present review, the role of zinc metabolism changes and its mechanisms in arterial hypertension are discussed.