Primary versus secondary events in hypertension.
Functional modifications, such as a reduction in hormonal response, which occur in the cardiovascular system in hypertension, are reflected at the cellular level by anomalies in cyclic nucleotide and other messenger systems. To distinguish between primary and adaptive abnormalities, we pursued three research strategies. (i) Investigations on various models of hypertension. To be considered a primary defect, an abnormality should also be present in other genetically hypertensive models. Indeed, we have confirmed the occurrence of cellular hyperplasia in the heart of spontaneously hypertensive rats (SHR) as well as in spontaneously hypertensive mice (SHM). An increase of calmodulin levels in the heart and kidney is also observed in both the SHR and SHM. (ii) Studies on the evolution of hypertension with age. In humans, a decrease of cAMP levels in response to beta-adrenergic stimulation in older patients is contrasted with an excess in younger subjects. In the SHR, protein kinase activity of the heart is lower in the prehypertensive stages, whereas this defect appears much later in the aorta. (iii) Experiments on anomalies in newborns and cultured cells. The heart and kidney in the SHR exhibit significant hyperplasia at birth, and an abnormal growth continues in tissue culture. We hope that these strategies will eventually help to provide biochemical and functional markers for genetic analysis of factors which may be involved in the pathogenesis of hypertension.
Hamet
P
P
Tremblay
J
J
Pang
S C
SC
Walter
S V
SV
Wen
Y I
YI
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001792:Blood Platelets / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002319:Cardiovascular System / Q000503:physiopathology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000097:blood; D006321:Heart / Q000503:physiopathology; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006965:Hyperplasia; D006973:Hypertension / Q000503:physiopathology*; D051379:Mice; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D002147:Calmodulin; D000242:Cyclic AMP