Autonomic and Renal Contributions to Hypertension With ADT

• Gonadotropin Releasing Hormone Agonists (GNRH) (Drug), also known as Leuprolide: 8 weeks of GnRH agonist
• Androgen receptor (AR) inhibitor (Drug), also known as Bicalutamide, Flutamide: 2 weeks of AR inhibitor
• Placebo (Drug): Placebo tablet and injection

Primary outcomes

• Change in cardiovagal baroreflex sensitivity [Before and after 9 weeks of ADT or placebo]: The change in cardiovagal baroreflex sensitivity will be assessed via the sequence method
• Change in blood pressure reactivity to the cold pressor test [Before and after 9 weeks of androgen deprivation therapy or placebo]: The change in systolic blood pressure will be assessed from quiet rest to sympathetic activation using the cold pressor test
• Change in exercise pressor reflex [Before and after 9 weeks of androgen deprivation therapy or placebo]: The change in systolic blood pressure will be assessed from quiet rest to isometric handgrip exercise
• Change in ambulatory blood pressure variability [Before and after 9 weeks of androgen deprivation therapy or placebo]: Ambulatory systolic blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring using the standard deviation of blood pressure readings
• Change in beat-to-beat blood pressure variability [Before and after 9 weeks of androgen deprivation therapy or placebo]: Beat-to-beat systolic blood pressure variability will be determined using the standard deviation of blood pressure readings from finger photoplethysmography measured in the laboratory.
• Change in renal vascular resistance [Before and after 9 weeks of androgen deprivation therapy or placebo]: Renal blood flow will be determined using ultrasound and blood pressure will be determined using finger photoplethysmography. These measures will be used to estimate renal vascular resistance.
• Change in kidney injury biomarkers [Before and after 9 weeks of androgen deprivation therapy or placebo]: Neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor binding protein 7 (IGFBP7) will be quantified in urine using commercially available assay kits. Concentrations will be normalized to urinary flow rate.

Sex: Male, ages: 40 Years to any, accepts healthy volunteers

Inclusion Criteria:

* age 40+ years;
* resting blood pressure <140/90 mmHg;
* fasted blood glucose <126 mg/dL;
* testosterone ≥400 ng/dL;
* sedentary to recreationally active;
* nonsmokers;
* healthy as determined by medical history, physical exam, blood and urine chemistries and resting and exercise ECG during a physician supervised graded exercise treadmill test OR recent diagnosis of non-metastatic prostate cancer with plans to undergo androgen deprivation therapy;
* PSA <4.00 ng/dL if in the non-cancer group;
* Gleason Score ≤7 if in the prostate cancer group;
* no use of medications that might influence cardiovascular function (e.g., antihypertensives, lipid-lowering medications);
* willing and able to be on GnRHagonist and AR inhibitor;
* not taking antioxidant vitamins, corticosteroids, or anti-inflammatory medications, or willing to stop use for four weeks prior to the start of the study;
* not using exogenous sex hormones for at least one year

Exclusion Criteria:

* -acute liver disease;
* chronic kidney disease, serum creatinine >1.3 mg/dL, macroalbuminuria >300 mg/g of proteinuria
* pre-existing or active cardiac, renal or hepatic disease, epilepsy or other seizure disorder;
* diabetes, active or chronic infection, disease that affects the nervous system;
* Gleason Score ≥8;
* thyroid dysfunction, defined as ultrasensitive TSH <0.5 or >5.0 mU/L, volunteers with abnormal TSH values will be re-considered for participation after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
* tobacco use within the previous 12 months

• Matthew Babcock, PhD, Principal investigator, Virginia Commonwealth University

NIH grants: K01HL164978