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Page 59
allied
academies
Nov 22-23, 2018 | Paris, France
Joint Event
Nutrition and Health
16
th
International Conference on
26
th
International Conference on
Diabetes and Endocrinology
&
Journal of Insights in Nutrition and Metabolism | Volume 2
Recent developments in the kallikrein-kinin system with hypertension and diabetes
J N Sharma
Kuwait University, Kuwait
D
iabetes has been implicated as a major risk factor in the
development of cardiovascular and renal complications.
Previous studies have indicated altered activities of the
bradykinin forming components in diabetic patients as well
as diabetic experimental animals. Type 2 diabetes can lead
to hypertension, renal and cardiac complications resulting
in high rates of mortality worldwide and in Kuwait as well.
Bradykinin (BK), a pharmacologically active polypeptide, is
one of kinins which is released in the tissues and body fluids
as a result of enzymatic action of kallikreins on kininogens.
The two types of kallikreins are tissue kallikrein and plasma
kallikrein. Tissue kallikrein is mainly expressed in the kidney
(urine), glandular tissue, vasculature, heart and brain. It
preferentially acts on low molecular weight kininogen
substrate to release lysyl-BK. Tissue kallikrein has also been
reported to be present in plasma. Plasma kallikrein acts
on high molecular weight kininogen substrate to release
BK. BK promotes both cardiovascular and renal functions,
for example, vasodilation, and diuresis (7,8). BK is rapidly
(< 15 sec) inactivated by circulating kinases (9). BK acts on
B1 receptors and B2 receptors to elicit physiological and
pharmacological actions. It has been shown previously
that type-1 diabetic patients are at a risk of developing
nephropathy. In addition, BK has been implicated in the
pathophysiology of hypertension. In this regard, it is
suggested that the role of renal BK is to excrete the excess
of sodium. Therefore, a reduction in the generation of renal
BK may be the cause in the development of hypertension
as a result of the accumulation of sodium in the body. Thus,
the development of a compound having renal kallikrein like
activity may serve the purpose of excreting excessive sodium
from the kidney in the treatment of hypertension. Transgenic
mice over expressing renal tissue kallikrein were hypotensive
and that administration of aprotinin, a tissue kallikrein
inhibitor, restored the BP of the transgenic mice. Recently,
it has been proposed that tissue kallikrein gene delivery
into various hypertensive models exhibits protection, such
as reduction in high blood pressure, attenuation of cardiac
hypertrophy, inhibition of renal damage and stenosis.
This may indicate the future therapeutics aspect of tissue
kallikrein gene therapy for hypertension, cardiovascular and
renal pathology. Abnormal BK and nitric oxide levels have
been demonstrated in diabetic patients in our study.
e:
j.n.sharma@hsc.edu.kw