Differences between the effect of nisoldipine and lisinopril on microvascular dysfunction in hypertensive IDDM patients with nephropathy

Purpose: Our objective was to compare the effect of a long-acting calcium-antagonist (nisoldipine) vs. an ACE-inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive IDDM patients with diabetic nephropathy. Methods: We performed a one year double-blind double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive IDDM patients with diabetic nephropathy. 22 age-matched controls were included for comparison. Measurements were performed at baseline and after one year of antihypertensive treatment. Blood pressure and the minimal vascular resistance (MVR) and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method with the isotopes ¹³³Xenon and ^99mTc-pertechnetate. The MVR and skin- and muscle distensibility were determined in a histamine- or papavarine-paralyzed vascular bed of the lower leg. Results: Mean arterial pressure was reduced to the same extend in both groups, nisoldipine: 113 ± 11 to 105 ± 8 mmHg (p < 0.001), lisinopril: 110 ± 13 to 101 ±10 mmHg (p < 0.002), (controls: 88 ± 9, p < 0.0001 for controls vs. diabetics). Nisoldipine improved the skin distensibility from 28 ± 17% to 43 ± 19% (p < 0.005) and decreased MVR from 16.9 ± 5.1.AU to 13.6 ± 3.8AU (p < 0.02). Lisinopril was without any significant effect on skin distensibility (40 ± 19% and 41 ± 21%) and MVR (18.1 ± 4.1AU and 15.8 ± 5.9AU (p = 0.09)). The control group had a skin distensibility 54±15% and a MVR of 10.8±3.0/4AU. Both significantly different from the diabetic group, p <0.0001. Skeletal muscle distensibility was unaltered after treatment with both drugs. In conclusion: Despite an equal reduction in systemic blood pressure only nisoldipine had a vasoprotective effect improving the abnormal arteriolar stiffness and minimal vascular resistance in the skin. This means better peripheral perfusion with unchanged systemic blood pressure and protection against development of ischemic skin lesions.