Oral treatment with low molecular weight heparin normalizes blood pressure in hypertensive rats.
Increased calcium uptake in vascular tissue, leading to elevated cytosolic free calcium has been implicated in the pathophysiology of hypertension. This study examined the effect of oral low molecular weight heparin (Logiparin) on systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in spontaneously hypertensive rats. Starting at age 12 weeks, spontaneously hypertensive rats were divided into three groups of six animals each. The drinking water of groups 1, 2 and 3 was replaced by 100% H2O, 0.5 mg (low dose) or 1 mg (high dose) low molecular weight heparin/ml H2O, respectively, for next 11 weeks. Six normotensive Wistar-Kyoto rats (age 12 weeks) on H2O and six on low dose heparin in H2O were used as controls. At age 23 weeks, increase in systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in spontaneously hypertensive rats was significantly lowered by low dose LMW heparin as compared to spontaneously hypertensive rats on H2O, but was significantly higher than Wistar-Kyoto rats on H2O and LMW heparin. This dose of heparin did not have any effect on these parameters in normotensive Wistar-Kyoto rats. High dose LMW heparin normalized the elevated platelet cytosolic free calcium, aortic calcium uptake and systolic blood pressure in spontaneously hypertensive rats, but it had a limited effect on adverse renal vascular changes. Oral low molecular weight heparin did not cause any abnormal hematological, biochemical or pathological changes in rats.
Department of Medicine and Laboratory Medicine, General Hospital, St. John's, Newfoundland, Canada.
S
S
Vasdev
C A
CA
Ford
L
L
Longerich
B
B
Barrett
S
S
Parai
N
N
Campbell
D000284:Administration, Oral; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001792:Blood Platelets / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects
D006495:Heparin, Low-Molecular-Weight; C079002:Logiparin; D002118:Calcium