Selective reduction of central pulse pressure under angiotensin blockage in SHR: role of the fibronectin-alpha5beta1 integrin complex.
BACKGROUND
Meta-analyses of antihypertensive therapy suggest that, independently of blood pressure (BP) level, stroke prevention is influenced mainly by calcium-entry blockers (CEB) and cardiac risk prevention by angiotensin-converting enzyme inhibitors (ACEIs). The possibility that central systolic and pulse pressure (PP) reduction differs between the two drug classes for the same mean BP (MBP) has never been explored. Our aim was to compare carotid PP at the same MBP obtained with the CEB, amlodipine, and the ACEI, trandolapril, in spontaneously hypertensive rats (SHR), and to evaluate the resulting changes of fibronectin (Fn) and its integrin alpha5beta1 receptor on central PP and arterial stiffness.


METHODS
Amlodipine and trandolapril were administered chronically to achieve the same MBP. Carotid arterial systolic BP (SBP) and PP, diameter and incremental elastic modulus (E(inc)) were determined using echo Doppler techniques, and complemented with vascular histomorphometry, and Fn and alpha5beta1-integrin immunolabeling.


RESULTS
Both drugs produced the same MBP, carotid wall thickness, and stress. Trandolapril reduced PP and E(inc) significantly more than amlodipine, while both agents comparably lowered EIIIA-Fn. Total Fn and alpha-subunit were lowered significantly by trandolapril, but unaffected by amlodipine, indicating that ACEI alone contributed to both diminished carotid stiffness and decrease of the Fn-integrin complex.


CONCLUSIONS
Results showed that amlodipine and trandolapril have different effects on carotid mechanical properties for comparable MBP reduction. Changes in Fn-integrin complex not only modify consistently ACEI mechanotransduction but also are associated with selective central PP reduction. Whether this property has consequences on cardiovascular (CV) risk remains to be investigated.
INSERM, Nancy, France.
Augustine
A
Kakou
Yvonnick
Y
Bézie
Nathalie
N
Mercier
Huguette
H
Louis
Carlos
C
Labat
Pascal
P
Challande
Patrick
P
Lacolley
Michel E
ME
Safar
D017311:Amlodipine / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005353:Fibronectins / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology*; D039081:Integrin alpha5beta1 / Q000502:physiology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D005353:Fibronectins; D007211:Indoles; D039081:Integrin alpha5beta1; D017311:Amlodipine; C052035:trandolapril