Angiotensin I-converting enzyme genotypes and angiotensin II receptors. Response to therapy.
In the present study, we studied angiotensin II type 1 (AT1) and type 2 (AT2) receptor messengers by quantitative reverse transcriptase-polymerase chain reaction. We examined peripheral blood mononuclear cells from 30 healthy subjects and 50 subjects with primary hypertension, in whom angiotensin I-converting enzyme genotype was determined, before and after 15 days of treatment with different antihypertensive drugs. The medication included a calcium channel antagonist, an angiotensin I-converting enzyme inhibitor, and a beta 1-blocker. We also studied the relationship between AT1 receptor gene expression and biochemical parameters of the renin-angiotensin system. AT1 receptor messenger levels were positively correlated with plasma renin activity in both normotensive and untreated hypertensive subjects. Increases of this messenger and plasma angiotensin II levels were correlated with the D allele in the same individuals. AT1 receptor messenger levels decreased significantly with angiotensin I-converting enzyme inhibitor treatment in subjects with the DD genotype, and a significant decrease was observed in subjects with the II and ID genotypes treated with a calcium antagonist. No changes were observed in mRNA with the beta 1-blocker. We conclude that the AT2 receptor is not expressed in peripheral leukocytes and that AT1 receptor messenger levels vary in relation to angiotensin I-converting enzyme genotype and pharmacological treatment. These results suggest that angiotensin I-converting enzyme genotype may be an important factor when deciding on antihypertensive therapy in individuals with primary hypertension.
Dieguez-Lucena
J L
JL
Departamento Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Málaga, Spain.
Aranda-Lara
P
P
Ruiz-Galdón
M
M
García-Villanova
J
J
Morell-Ocaña
M
M
Reyes-Engel
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000804:Angiotensin II / Q000235:genetics*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D011945:Receptors, Angiotensin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D005819:Genetic Markers; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A