Hypertention

Hypertension

    

• R
  Troost, E Schwedhelm, S. Rojczyk, et al (Institute
  of Clinical Pharmacology, Germany).
  
  Nebivolol
  decreases systemic oxidative stress in healthy
  volunteers.
  
  Br.
  J.Cl.Pharmacol, Oct.2000; 50(4), 377-379
  
    
  
  Summary:
  Nebivolol is a vasodilating and highly selective
  B1-adrenoceptor antagonist with additional
  antioxidative effects.
  
    
  
  Isoprostanes
  are prostaglandin (PG) like compounds which are
  produced from arachidonic acid.
  8-iso PGF_2a
  is one of such isoprostanes formed in-vivo and is
  increased during experimentally induced oxidative
  stress and in atherosclerosis.
  
   
  
  Whether
  nebivolol decreases oxidative stress after oral
  therapeutic antihypertensive dose in man has not
  been investigated. 
  The present study was to determine the effect
  of nebivolol on systemic oxidative stress by
  measuring urinary excretion of 8-iso-PGF_2a
  in healthy volunteers.
  
   
  
  The
  study has demonstrated that oral administration of
  nebivolol at standard antihypertensive doses
  decreases significantly urinary excretion of the
  isoprostane 8-iso-PGF_2a.
  This strongly supports the hypothesis that
  nebivolol exerts systemic anti-oxidant effects. This provides a rationale for further clinical studies on
  antioxidative effects of nebivolol in cardiovascular
  disease.
  
     

• Emma
  H Baker (Department of Pharmacology and Clinical
  Pharmacology, St. George’s Hospital Medical School,
  London, UK)
  
  Ion
  channels and the control of blood pressure.
  
  Br.
  J.Clin. Pharmacol, 49, 185-198.
  
   
  
  Summary:
  Ion channels are found in living cells and their
  normal function is vital for life.
  They are actively involved in determining
  movement of ions into and out of cells and are
  central to homeostasis.
  The term ‘channelopathies’ is coined to group
  diseases caused by ion-channel abnormalities.
  Ion channels are targets for action of drugs
  to treat multifactorial conditions such as
  hypertension.
  
    
  
  The
  review deals with structure and function of
  ion-channels. As
  regards control of blood pressure, role of
  epithelial sodium channels, renal outer medullary
  potassium channel and ion channels in vascular
  smooth muscles are discussed.
  
    
  
  Drug
  treatment for hypertension: Calcium channel blocking
  drugs and potassium channel opening drugs close
  voltage-gated calcium channels, reduce calcium
  influx into smooth muscle cells and relax vascular
  smooth muscle. Drugs
  blocking L-type calcium channels (e.g. nifedipine)
  are known for over 30 years.
  T-type calcium channels also play a role in
  control of blood pressure and are involved in growth
  and proliferation of vascular smooth muscle cells.
  Mibefradil blocks both T and L-type of Ca⁺⁺
  channel blockers may control blood pressure
  and also prevent or reverse hypertension induced
  cardiovascular remodelling that may contribute to
  morbidity and mortality of hypertension.
  
       
  
  Potassium
  channel openers : They are classified according to
  their actions into (1) agents which open
  ATP-sensitive K⁺ channels – e.g.
  cromokalin, pinacidil (2) agents which activate
  guanylate cyclase in addition to ATP-sensitive K⁺
  channels – e.g. nicorandil (3) agents which open
  calcium dependent K⁺ channels e.g.
  dehydrosaporin.
  
      
  
  Pinacidil
  is available in several countries for treatment of
  hypertension but may cause oedema, tachycardia,
  headache or palpitations.
  Nicorandil is an arteriolar and venous
  dilator and increases coronary blood flow – used in
  prevention and treatment of angina.
  
       
  
  Experimental
  studies suggest that K+ channels play a role in
  development of shock.
  Glibenclamide, which blocks ATP-sensitive K+
  channels raised blood pressure in experimental 
  endotoxin induced and haemorrhagic shock. This suggests that drugs which block K+ channels may have a
  therapeutic role in management of shock.
  
       

•  Jan A Staessen, Ji-Guang Wang, Lutgarde Thijs 
  
  Cardiovascular Protection and Blood Pressure Reduction: A Meta-Analysis 
  
  The Lancet October 20, 2001, Vol.358 (9290) Pg. 1305-1315
  
       
  
  
  The authors’ conducted a meta-analysis of nine randomised trials comparing treatments in 62 605 hypertensive patients. Compared with old drugs (diuretics and b-blockers), calcium-channel blockers and angiotensin converting-enzyme inhibitors offered similar overall cardiovascular protection, but calcium-channel blockers provided more reduction in the risk of stroke (13.5%, 95% Cl 1.3-24.2, p=0.03) and less reduction in the risk of myocardial infarction (19.2%, 3.5-37.3, p=0.01). 
  
       
  
  
  The authors’ findings emphasise that blood pressure control is important. All antihypertensive drugs have similar long-term efficacy and safety.