Alpha-Adrenoceptor Vascular Function In Chronic Kidney Disease Focus On The Role Of Endothelial Nitric Oxide
| Status: | Terminated |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 1/25/2018 |
| Start Date: | July 2006 |
| End Date: | November 2010 |
The purpose of this study is to learn more about why most patients with early stages of
kidney disease have high blood pressure.
We know the body produces natural substances that cause blood vessels to open wider to carry
more blood when needed. An example is during exercise. Other natural substances cause blood
vessels to get smaller and slow down blood flow when needed. An example is when people are
cold. The balance between these substances is important. People with kidney disease and high
blood pressure do not have the normal balance of these substances.
This study will include 3 groups of people, people with normal blood pressure, people with
high blood pressure and people with kidney disease.
- Subjects will have a screening physical examination, including an ECG and laboratory
tests
- Subjects with high blood pressure may not take their regular blood pressure medication
for 3 weeks prior to the inpatient GCRC study
- Subjects will be given intra-arterial medications that will cause changes in the blood
vessels during the in-patient study.
The study will then compare the responses of the three groups. A GFR test will be done to
confirm the renal function of the group with chronic kidney disease.
These studies will provide insight into the mechanisms of the pathogenesis of enhanced α1
vasoreactivity in subjects with progressive renal disease. This will lay the groundwork for
new strategies in the treatment and prevention of vascular disease among the rapidly growing
group of individuals with CKD.
kidney disease have high blood pressure.
We know the body produces natural substances that cause blood vessels to open wider to carry
more blood when needed. An example is during exercise. Other natural substances cause blood
vessels to get smaller and slow down blood flow when needed. An example is when people are
cold. The balance between these substances is important. People with kidney disease and high
blood pressure do not have the normal balance of these substances.
This study will include 3 groups of people, people with normal blood pressure, people with
high blood pressure and people with kidney disease.
- Subjects will have a screening physical examination, including an ECG and laboratory
tests
- Subjects with high blood pressure may not take their regular blood pressure medication
for 3 weeks prior to the inpatient GCRC study
- Subjects will be given intra-arterial medications that will cause changes in the blood
vessels during the in-patient study.
The study will then compare the responses of the three groups. A GFR test will be done to
confirm the renal function of the group with chronic kidney disease.
These studies will provide insight into the mechanisms of the pathogenesis of enhanced α1
vasoreactivity in subjects with progressive renal disease. This will lay the groundwork for
new strategies in the treatment and prevention of vascular disease among the rapidly growing
group of individuals with CKD.
Enhanced adrenergic vascular reactivity may significantly contribute to hypertension and the
excessive cardiovascular disease burden in patients with chronic kidney disease (CKD). Nitric
oxide (NO), a modulator of neurovascular function, may be linked to adrenergic vascular
responsiveness. The central HYPOTHESIS is that the reduction in endothelial nitric oxide (NO)
bioavailability contributes to the enhancement of α1-adrenoceptor vasomotor function in
patients with CKD.
Specific Aims: In patients with mild to moderate CKD, compared to matched hypertensive and
normotensive controls without CKD:
1. Determine if α1-adrenoceptor vasoreactivity is enhanced less by inhibition of
endothelial NO
2. Determine whether α1-adrenoceptor vasoreactivity correlates with plasma levels of the
endogenous NO inhibitor, asymmetrical dimethylarginine.
Methods: CKD will be confirmed by I125-iothalamate glomerular filtration rate. Regional
α1-adrenoceptor vasoreactivity (sensitivity [EC50], reactivity [slope]) will be assessed by
venous plethsymography using a graded intra-arterial infusion of the α1-adrenoceptor agonist,
phenylephrine. Comparisons of vasoreactivity at baseline and during infusions of L-NMMA will
be made between hypertensive non-diabetic subjects with glomerular filtrations rates between
30-70 ml/min age-, gender-, ethnicity- and % body fat-matched hypertensive and normotensive
subjects with normal kidney function. In addition, plasma levels of the endogenous NO
inhibitor, asymmetric dimethylarginine will be measured in the hypertensive subjects with and
without CKD and compared to vasoreactivity.
Significance. These studies will provide insight into the mechanisms of the pathogenesis of
enhanced α1 vasoreactivity in subjects with progressive renal disease.
excessive cardiovascular disease burden in patients with chronic kidney disease (CKD). Nitric
oxide (NO), a modulator of neurovascular function, may be linked to adrenergic vascular
responsiveness. The central HYPOTHESIS is that the reduction in endothelial nitric oxide (NO)
bioavailability contributes to the enhancement of α1-adrenoceptor vasomotor function in
patients with CKD.
Specific Aims: In patients with mild to moderate CKD, compared to matched hypertensive and
normotensive controls without CKD:
1. Determine if α1-adrenoceptor vasoreactivity is enhanced less by inhibition of
endothelial NO
2. Determine whether α1-adrenoceptor vasoreactivity correlates with plasma levels of the
endogenous NO inhibitor, asymmetrical dimethylarginine.
Methods: CKD will be confirmed by I125-iothalamate glomerular filtration rate. Regional
α1-adrenoceptor vasoreactivity (sensitivity [EC50], reactivity [slope]) will be assessed by
venous plethsymography using a graded intra-arterial infusion of the α1-adrenoceptor agonist,
phenylephrine. Comparisons of vasoreactivity at baseline and during infusions of L-NMMA will
be made between hypertensive non-diabetic subjects with glomerular filtrations rates between
30-70 ml/min age-, gender-, ethnicity- and % body fat-matched hypertensive and normotensive
subjects with normal kidney function. In addition, plasma levels of the endogenous NO
inhibitor, asymmetric dimethylarginine will be measured in the hypertensive subjects with and
without CKD and compared to vasoreactivity.
Significance. These studies will provide insight into the mechanisms of the pathogenesis of
enhanced α1 vasoreactivity in subjects with progressive renal disease.
Inclusion Criteria:
- Men and Women-18 to 55 years of age.
- There are three groups of volunteers.
- Group A. People who are hypertensive with kidney disease. When not taking blood
pressure medicines, blood pressure must have a systolic between 140-170 mmHg.
Diastolic must be between 90-109 mmHg.Kidney function should be around half of
normal. Urine protein must be no more than 1 gram in a 24-hour urine time period.
- Group B. People who are hypertensive without kidney disease. Blood pressure must
have a systolic between 140-170 mmHg. Diastolic must be between 90-109 mmHg.
Kidney function should be normal. Normal amounts of protein in their urine.
- Group C. People who are normotensive. Blood pressure must have a systolic below
131/mmHg. Diastolic must be below 81 mmHg. Kidney function should be normal. No
more than normal amounts of protein in their urine.
Exclusion Criteria:
People with:
- Diabetes
- Lung disease
- Stomach disease
- Liver disease
- Blood vessel disease
- Heart disease
- Hereditary blood disorders
- Hematocrit (amount of red blood cells) less than 30%
- Current tobacco use
- Kidney disease who require dialysis
- Women who are pregnant or breastfeeding
We found this trial at
1
site
Click here to add this to my saved trials
