Muscle Cells Of Resistance Vessels Research Articles

Sympatho-modulatory therapies in perioperative medicine

With increasing life expectancy and improved surgical technology an ever-larger number of elderly patients with cardiovascular disease, or significant cardiovascular risk factors will undergo major surgery. More than 5% of an unselected surgical population undergoing non-cardiac surgery will suffer from perioperative cardiovascular complications including myocardial infarction and cardiac death. The incidence of adverse cardiac events may even reach 30% in high-risk patients undergoing vascular surgery causing a substantial financial burden of perioperative health care costs. 59 Thus, all therapeutic measures should be undertaken to reach the challenging goal of a lower incidence of perioperative cardiovascular complications. Gaining control over sympathetic nervous system activity, that is blunting the adrenergic response to the surgical trauma, traditionally represents an important aspect of anaesthetic practice. 21 Anaesthesiology has been regarded as the ‘practice of autonomic nervous system medicine’. While variable and moderate changes in sympathetic nervous system activity function as a servo-control mechanism and are even required to maintain and optimize cardiac performance, undue liberation of excitotoxic substances such as catecholamines and inflammatory cytokines, particularly during emergence from anaesthesia and the painful postoperative period, facilitates the occurrence of cardiovascular complications. 83 84 At this point, the life-supporting adrenergic drive (‘fight-or-flight-response’) turns into a potentially hazardous life-threatening maladaptation. In support of this concept, the beneficial effects of antiadrenergic treatment regimens in perioperative medicine have been confirmed, in observational studies, metaanalyses 55 1 66 and randomized controlled clinical trials. 43 54 59 63 80 84 However, the seemingly established concept of ‘sympatholysis’ as an effective cardioprotective treatment modality needs considerable refinement in the light of the many new experimental and clinical findings. The parlance of ‘sympatholytic’ protection erroneously equates annihilation of any type of adrenergic stimulation with cardioprotection and should be replaced by ‘sympathomodulatory’protection. The present review summarizes findings from large-scale heart failure trials and discusses basic and clinical aspects of individual sympatho-modulatory therapies, as currently used in perioperative medicine, including b-adrenergic antagonism, a2-agonism, and regional anaesthetic techniques. For limitation of space, reviews will often be cited where further references to the primary literature may be found.

Structural and functional alterations of mesenteric vascular beds in spontaneously hypertensive rats.

The morphology and reactivity of mesenteric arteries from spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY) were investigated. Isolated, perfused mesenteric vascular beds were prepared from 6-, 11- and 18-week-old SHR and WKY. At these ages, the walls and media of large mesenteric arteries were significantly thicker in SHR than in WKY. The number of smooth muscle cell layers in the media was significantly larger in SHR than in WKY. This difference between SHR and WKY increased as rats grew older, in parallel with differences in the blood pressure. Flow rate-perfusion pressure curves indicated that the vascular basal resistance to flow increased more profoundly in SHR preparations than in WKY preparations as rats grew older. This may be related to the structural alterations of the resistance vessel wall in SHR. The pressor responses to KCl were greater in SHR preparations than in WKY preparations as rats grew older. This may be caused partly by the increase of the number of smooth muscle cell layers in the media of SHR resistance vessels. The pressor response to norepinephrine (NE) was significantly higher in SHR preparations than in WKY preparations at all ages investigated. In marked contrast to the vascular basal resistance and the pressor response to KCl, the pressor response to NE was extremely exaggerated in SHR at the age of 6 weeks. This extremely high NE response in younger SHR may not be caused by the structural alteration in resistance vessels. It may be caused by a functional change, which is regulated by the signal transduction process in smooth muscle cells of resistance vessels. These results suggest that the development of hypertension in SHR may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by the hyperreactivity to NE through an altered signal transduction process in smooth muscle cells of resistance vessels in SHR.

Possible Mechanisms of Abnormal Norepinephrine Sensitivity and Reactivity of Resistance Vessels and the Development of Hypertension in Spontaneously Hypertensive Rats: A Hypothesis

This study examined structural and functional changes of mesenteric resistance vessels in early, developing, and established stages of hypertension development in spontaneously hypertensive rats in an attempt to identify possible mechanisms of the development and maintenance of hypertension. Our results suggest that the development of hypertension in spontaneously hypertensive rats may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by hyperreactivity to norepinephrine through an altered signal transduction process, including the regulation of protein kinase C in smooth muscle cells of resistance vessels in spontaneously hypertensive rats.

Coronary flow increases induced by adenosine and adenine nucleotides are mediated by the coronary endothelium: a new principle of the regulation of coronary flow.

Intracoronary adenosine as well as the adenine nucleotides (ATP, ADP, AMP, beta, gamma-methylene-ATP, diadenosine-tetraphosphate, and polyadenylic acid) do not elicit their dilatory effects directly at the smooth muscle cells of the resistance vessel wall, but indirectly, via the endothelium. This must be concluded, since for these compounds the coronary endothelium represents an impermeable barrier between intra-arterial and intra-capillary spaces on the one hand, and the interstitium on the other. Furthermore, in equimolar concentrations the substances investigated induce quantitatively very similar increases in flow, although they are characterized by a highly differing metabolism during their passage through the coronary system as well as by great differences in molecular weight. These endothelium-dependent reactions cannot be influenced by 10(-4)M methylene blue, 10(-5)M haemoglobin, or pre-perfusion with 10(-6)M indomethacin. Accordingly, neither the EDRF nitric oxide nor PGI2 can be considered to be the mediator of these particular increases. There are now, however, observations indicating that the coronary endothelium and the smooth muscle cells of the coronary resistance vessels act as an electrically communicating 'syncytium'. In the light of these recent discoveries, a new principle of coronary flow regulation is suggested.

Ploidy in mesenteric vessels of aged spontaneously hypertensive and Wistar-Kyoto rats.

Long-term regulation of blood pressure in a hypertensive rat may be mediated by elevated DNA content of smooth muscle cells of resistance vessels. This study explores DNA changes represented by an increased frequency of polyploid cells in multiple levels of the mesenteric arterial tree of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) control rats. Two ages were examined: 45 and 78-80 weeks of age. SHR and WKY rats did not differ in frequency of polyploid cells at any mesenteric branch level at either age. Although hypertension per se seemed not to be a factor, both species showed increased numbers of polyploid cells with aging at certain branch levels of the mesenteric arterial tree. The data in the current study support the idea that hypertension and aging may result in similar and possibly additive changes in DNA in the vessel wall.

The Na+/H+ antiport, cytosolic free Ca2+, and essential hypertension: a hypothesis.

We propose that in essential hypertension higher cytosolic free Ca2+ ([Ca2+]i) is associated with hyperactivity of the Na+/H+ antiport and that augmented activity of this transport system explains at least some abnormalities in Na+ metabolism associated with this disease. In low-renin essential hypertension, a higher [Ca2+]i is present not only in vascular smooth muscle cells of resistance vessels but also in juxtaglomerular cells and renal proximal tubular epithelium. A higher [Ca2+]i in juxtaglomerular cells retards renin secretion, whereas in renal proximal tubules it is associated with increased Na+ reabsorption via the Na+/H+ antiport. Thus, hyperactivity of the Na+/H+ antiport in renal tubular epithelium may be the cause of salt (NaCl) sensitivity. Ca2+ antagonists probably exert their antihypertensive effect by reducing [Ca2+]i in both vascular smooth muscle cells and renal tubular epithelium. These agents are, therefore, particularly effective in the treatment of essential hypertension in blacks and older individuals with the low-renin form of the disease, who are known to be salt sensitive.

Immunohistochemistry of the renin-angiotensin-system in the kidney.

Changes of the intrarenal localization and concentration of renin in comparison to those of angiotensin II (ANG II) are shown under various conditions of stimulation and inhibition of the renin-angiotensin-system. Evidence is presented that ANG II which is detectable by immunocytochemical methods in epitheloid cells is formed locally within the kidney either intra- or extracellularly. ANG II-like activity was found not only in the epitheloid cells of the JGA, but also further upstream in non specialized, "plain" smooth muscle cells of the renal arterial tree and in the medial muscle cells of resistance vessels in other organs and tissues. This ANG II-like activity of resistance vessels is increased in spontaneously hypertensive rats suggesting a possible role in the long-term regulation of blood pressure.

Angiotensin-like activity in resistance vessels. Immunocytochemical study in Chinese hamsters.

Angiotensin II (ANG II) was localized immunocytochemically in kidney and various other organs of the chinese hamster. In the kidney ANG II-like activity was found in the epitheloid cells of the juxtaglomerular apparatus as well as in the media i.e. the smooth muscle cells of arcuate and interlobular arteries and afferent arterioles. ANG II-like activity was also observed in the medial muscle cells of resistance vessels in other organs and tissues such as submandibular gland and brown adipose tissue. The site of synthesis of ANG II needs to be investigated but the data point to the possibility of an intracellular function of ANG II in smooth muscle cells of blood vessels.