Effects of continuous intermedin infusion on blood pressure and hemodynamic function in spontaneously hypertensive rats.
OBJECTIVE
To examine the effects of exogenously administered intermedin (IMD, adrenomedullin-2) on arterial blood pressure, cardiac function and the cardiovascular IMD receptor system in spontaneously hypertensive rats (SHRs) as well as to investigate the associated mechanisms.


METHODS
Thirteen week-old male rats were divided in Wistar Kyoto (WKY) group (n = 12), SHR group (n = 12), IMD group (SHRs infused with IMD 1-47 500 ng/kg per hour, n = 12), and ADM group (SHRs infused with adrenomedullin 500 ng/kg per hour, n = 12).


RESULTS
A two-week continuous administration of low dose IMD 1-47 via mini-osmotic pumps markedly reduced blood pressure, the maximal rates of increase and decrease of left-ventricle pressure development (LV ± dp/dt(max)), left ventricular systolic pressure and heart rate in SHRs. Furthermore, IMD also inhibited protein over-expression of cardiovascular IMD receptors, myocardial Receptor Activity-Modifying Proteins (RAMP1 and RAMP2), aortic RAMP1, RAMP2, RAMP3, and calcitonin receptor-like receptor (CRLR); suppressed up-regulation of aortic RAMP1, RAMP2, RAMP3 and CRLR gene expression; and markedly elevated the mRNA abundance of myocardial atrial natriuretic peptide (ANP) and myocardial brain natriuretic peptide (BNP). Additionally, IMD 1-47 administration in SHRs increased aortic cAMP concentration and reduced myocardial cAMP concentration.


CONCLUSIONS
These findings support the speculation that IMD, as a cardiovascular active peptide, is involved in blood pressure reduction and cardiac function amelioration during hypertension. The mechanism underlying this effect may involve IMD binding of a receptor complex formed by RAMPs and CRLR, and consequential regulation of cAMP levels and other cardiovascular active factors, such as ANP and BNP.
Human Centrifuge Medical Training Base of Institute of Aviation Medicine, Air Force, Beijing 100089, China.
Ying
Y
Yuan
Xi
X
Wang
Qiang
Q
Zeng
Hong-Mei
HM
Wu
Yong-Fen
YF
Qi
Chao-Shu
CS
Tang