Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Preface to Second Edition -- Part I Basic science -- 1 Vascular tone -- Introduction -- Types of stimulus for contraction and relaxation -- Agents acting at G protein-coupled receptors -- Pressure/tension -- Agents acting directly on ion channels or signalling systems -- Extracellular matrix components, cell adhesion molecules and integrins -- Growth factors -- Regulation of [Ca2+]i in vascular smooth muscle -- Ca2+ influx -- Ion channels, membrane potential and [Ca2+]i -- Major ion channel species in vascular smooth muscle -- K channels -- Cl channels -- Voltage-operated sodium channels -- Voltage-operated calcium channels -- Calcium (cation) channels -- Intracellular calcium stores -- Calcium efflux: Ca-ATPase, Na/Ca exchange -- The ultrastructure of the contractile apparatus in smooth muscle -- How increased [Ca2+]i initiates contraction -- Force generation in smooth muscle: actin-myosin interaction -- Sensitization and desensitization of the contractile machinery to [Ca2+]i -- Biochemical mechanisms of sensitization and desensitization -- Phospholipase C, protein kinase C and lipid-derived signals -- Protein phosphatases -- Regulation of MLCP -- Cyclic nucleotides -- Actin-associated proteins: caldesmon and calponin -- Latch state -- Conclusions -- REFERENCES -- 2 Vascular compliance -- Introduction -- Definitions and terminology -- Influence of large artery compliance on systemic haemodynamics -- Measurement of arterial compliance -- Biomechanical determinants of compliance: arterial wall structure -- Alterations in large artery compliance in physiological conditions -- Ageing, pregnancy and the menopause -- Vascular structural change in pregnancy -- Influence of oestrogen -- Alterations in arterial compliance in vascular disease -- Hypertension.

Other conditions associated with altered large artery stiffness -- Increased aortic stiffness as a cardiovascular risk factor -- Interventions to modify large artery stiffness -- Conclusion -- REFERENCES -- 3 Flow-mediated responses in the circulation -- Introduction -- Flow and vascular tone -- Shear evokes relaxation through nitric oxide and prostacyclin release -- Vasodilatation to flow in vascular disease -- The endothelial cell as a mechanotransducer -- The cytoskeleton as a mechanotransducer -- G proteins as mechanosensors -- Ion channels as mechanosensors -- Shear stress-sensitive gene expression -- Vascular permeability and hydraulic conductivity in response to shear -- Flow, vascular remodelling and atherosclerosis -- Conclusion -- REFERENCES -- 4 Neurohumoral regulation of vascular tone -- Introduction -- Hormonal control of the vasculature -- Localization of vascular receptors -- Catecholamines -- Angiotensins -- Vasopressin -- Endothelin -- Urotensin -- Atrial natriuretic peptide -- Purines -- Vascular nerves and neurotransmitters -- Localization of vascular nerves -- Localization of neurotransmitters -- Transmitter release and smooth muscle activation -- Cotransmission -- Vascular modulation by neurotransmitters -- Vasoconstrictor nerves -- Vasodilator nerves -- Modulation of sympathetic neurotransmission -- Summary -- REFERENCES -- 5 Angiogenesis: basic concepts and the application of gene therapy -- Introduction -- Basic cellular mechanisms of angiogenesis -- Methods of studying angiogenesis -- In vitro -- In vivo -- In situ -- Quantification of angiogenesis -- Mediators of angiogenesis and antiangiogenesis -- Mechanical -- Factors -- Physiological and pathological angiogenesis -- Gene therapy and its current application to angiogenesis -- Ischaemic heart disease -- Peripheral vascular disease.

Tumour treatment and the inhibition of angiogenesis -- The future of therapeutic angiogenesis and antiangiogenesis -- REFERENCES -- 6 The regulation of vascular smooth muscle cell apoptosis -- Introduction -- Apoptosis: defining the mode of cell death -- Cell proliferation and death in the vascular wall -- Remodelling -- Arterial injury -- Aneurysm formation -- Atherosclerosis -- Effect of VSMC apoptosis -- Regulation of VSMC apoptosis -- Apoptosis via death receptors -- Apoptosis via mitochondrial amplification -- Inhibition of death receptor-induced apoptosis -- How important is death receptor-induced apoptosis in VSCMs? -- Bcl-2 family members and VSMC apoptosis -- Summary -- REFERENCES -- 7 Wound healing: laboratory investigation and modulating agents -- Wound healing: an overview -- Wound healing: early events -- Role of inflammatory cells -- Role of inflammatory cells -- Wound healing: central events -- Roles of the fibroblast -- Migration -- Extracellular matrix contraction -- Proliferation -- Role of endothelial cells -- Role of epithelial cells -- Wound healing: late events -- ECM production and remodelling -- Role of growth factors in wound healing -- Modulation of wound healing -- Immunosuppressives/antiinflammatories -- Antimigration/anticytoskeletal agents -- Antiproliferative/antimetabolic agents -- Inhibitors of angiogenesis -- Agents affecting ECM synthesis and degradation -- Agents affecting growth factors and growth factor receptors -- REFERENCES -- Part II Pathophysiology: mechanisms and imaging -- 8 Genes for hypertension -- Patterns of inheritance in essential hypertension -- Genetic susceptibility to raised blood pressure -- Environmental factors for raised blood pressure -- Family study designs used in hypertension -- Affected sibling pair methods -- Extreme discordant sib pairs -- Transmission disequilibrium testing.

Population association or case-control studies -- Rare hypertensive phenotypes: clues for essential hypertension -- Epithelial sodium channel, Liddle's syndrome and hypertension -- Genetic clues from hypertensive models -- Comparative mapping: rat hypertensive loci translated to humans -- Candidate genes in rats guide studies in humans -- Candidates for human hypertension -- The angiotensinogen gene locus: analysis in humans -- Gene targeting and angiotensinogen: the synthetic experiments -- Angiotensinogen: a definitive cause for hypertension or false positive? -- G protein variant alters sodium exchange -- Candidates from the sympathetic nervous system -- Genome-wide screens in human hypertension -- Hypertension genetics: quo vadis? -- Acknowledgements -- REFERENCES -- 9 The endothelium in health and disease -- Introduction -- Endothelial cell activation -- The changes in endothelial cell activation -- Loss of vascular integrity -- Expression of leukocyte adhesion molecules -- Cytokine production -- Prothrombotic changes -- Antiplatelet/vasoactive effects -- Anticoagulant pathways -- Procoagulant effects -- Fibrinolytic effects -- Upregulation of expression of class I and II HLA molecules -- The intracellular mechanisms underlying endothelial cell activation -- Endothelial cell activation in disease -- Systemic inflammatory response syndrome (SIRS) -- Ischaemia-reperfusion injury -- Antiendothelial cell antibodies -- Immune complexes -- Summary -- Endothelial responses to hypoxic stress -- The oxygen sensor -- Second messenger systems -- Genes upregulated by hypoxia in the endothelium -- Vascular endothelial growth factor -- Endothelial nitric oxide synthase (eNOS) and NO -- In vivo effects of chronic hypoxia -- Endothelial cell heterogeneity -- REFERENCES -- 10 Nitric oxide -- Introduction -- From EDRF to nitric oxide.

The L-arginine-nitric oxide pathway -- Nitric oxide synthase isoforms: expression and regulation -- Regulation by calcium and calmodulin -- Caveolae -- Acylation -- Phosphorylation -- Regulation by shear stress -- Ultraquick:ion channels -- Quick: phosphorylation -- Slow: increased transcription -- Agonist activation of eNOS -- Genetic variation in NOS isoforms -- Biological effects of NO on the vasculature -- Nitric oxide release from the vascular endothelium -- Basal nitric oxide release -- Agonist-stimulated NO release -- Vascular phenotype of NOS knockouts -- eNOS -- nNOS -- iNOS -- Limitations of knockout studies -- Assessing NO response using acetylcholine -- Biochemical detection of NO in vivo -- Loss of NO and predisposition to atherogenesis -- Endothelial dysfunction in disease states -- Hypercholesterolaemia and atherosclerosis -- Hypertension -- Diabetes mellitus -- Links between risk factors and atherogenesis -- Chronic heart failure -- How might diseases alter the L-arginine-NO pathway? -- Decreased NO production -- Cofactor deficiency -- Role of endogenous inhibitors of NOS -- Decreased NO bioavailability -- Role of oxidative stress -- Advanced glycation endproducts -- Decreased VSMC sensitivity -- Endotoxaemia, septic shock and inflammation: overproduction of NO -- Future therapeutic possibilities -- Potential therapies to increase NO production -- L-arginine -- The arginine paradox -- Nitrovasodilators/NO donors -- Inhalation of NO -- Antioxidants -- Gene transfer -- Potential therapies to decrease NO production -- NOS inhibitors -- REFERENCES -- 11 Magnetic resonance imaging in vascular biology -- Introduction -- Imaging -- Catheter angiography -- CT scanning -- Ultrasound scanning -- Magnetic resonance imaging -- MRI techniques -- Morphology: established disease -- Vessel lumen: MR angiography (MRA) -- Time-of-flight angiography.

Contrast-enhanced angiography.