Measurement of left ventricular maximal isovolumetric pressure in rats: effects of antihypertensive drugs and diabetes mellitus.
We developed a method for measuring left ventricular maximal isovolumetric pressure (LVMIP) in intact rats and applied it in the presence of acutely administered antihypertensive drugs and in experimental diabetes mellitus. The combination of a 2 French Fogarty arterial embolectomy balloon catheter with a new ultra-thin shaft (0.25 mm diameter) Millar ultra-miniature pressure tip catheter was used. Closed-chest, thiopental anaesthetized female Sprague-Dawley rats received the beta-adrenoceptor blocker metoprolol (1 mg/kg/h), the alpha-adrenoceptor blocker prazosin (0.1 mg/kg/h), and the calcium antagonist nifedipine (0.5 mg/kg/h). They were applied as continuous i.v. infusion for 30 minutes. The angiotensin II type 1 (AT1) receptor antagonist losartan (3 mg/kg) was applied as bolus i.v. injection. Diabetes mellitus was induced by a single tail vein injection of streptozotocin (60 mg/kg) five weeks prior to hemodynamic measurements. Under control conditions, left ventricular systolic pressure (LVSP) was 136.5 +/- 3.7 mmHg and increased to 263 +/- 5.4 mmHg when the balloon was inflated (LVMIP). LVSP was significantly lower in the presence of prazosin, metoprolol, nifedipine, and in diabetic rats. However, LVMIP was significantly reduced only in the metoprolol-treated and diabetic rats. Both LVSP and LVMIP did not change significantly in losartan-treated rats. The degree of the increase in left ventricular maximal isovolumetric pressure during balloon inflation (LVMIP-LVSP) was not significantly different in any experimental condition. These results suggest that the mechanism for evoking LVMIP is not dependent on the acute stimulation of cardiac alpha- and beta-adrenergic receptors, on calcium channels, nor on the AT1 receptors. In addition, the intrinsic mechanism for the generation of LVMIP seems not to be influenced in the diabetic state.
Iwai
T
T
Department of Medicine, Jikei University School of Medicine, Tokyo, Japan.
Irlbeck
M
M
Zimmer
H G
HG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001795:Blood Pressure Determination; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002404:Catheterization; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D019808:Losartan / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D008790:Metoprolol; D009543:Nifedipine; D019808:Losartan; D011224:Prazosin